A team of Johns Hopkins researchers is calling for magic mushrooms to be made legally available as medicine

  • A group of Johns Hopkins University scientists wrote in a recent journal article that psilocybin, the active ingredient in psychedelic magic mushrooms, has a low risk of harm and a high potential as a therapeutic drug.
  • Pending results from several ongoing clinical trials, the researchers called for psilocybin to be placed in the most lenient category by the Drug Enforcement Administration — alongside CBD, which was rescheduled last month, and cough syrup.

It’s not every day that a team of top-notch scientists calls for an illegal psychedelic drug to be made available as medicine.

But earlier this year, some of the leading researchers at Johns Hopkins University — people who’ve pioneered some of the highest-caliber studies on psychedelics’ therapeutic mental health potential— suggested that’s what should happen for a drug derived from magic mushrooms.

In a recent article published in the medical journal Neuropharmacology, four preeminent psychiatrists wrote that psilocybin, the active ingredient in magic mushrooms, should be placed in the most lenient category by the Drug Enforcement Administration and made legally available through clinicians, pending final data from several ongoing clinical trials.

In essence, they argue, the potential benefits presented by psilocybin outweigh its possible harms.

The available evidence suggests they’re correct.

Although the DEA currently considers psilocybin a Schedule I drug “with no medical use,” the past decade has seen a resurgence of research on psychedelics’ therapeutic possibilities for treating psychiatric diseases like anxiety and depression. A large recent survey also suggested that magic mushrooms could be among the safest recreational drugs.

That suggests to several experts — including the authors of the recent article — that psilocybin should be handled differently than, say, heroin or bath salts (other Schedule I drugs).

“It is the opinion of the authors of this review that the original placement of psilocybin was the result of a substantial overestimation of the risk of harm and abuse potential,” they wrote.

The authors included Johns Hopkins University School of Medicine professors of psychiatry Matthew Johnson, Roland Griffiths, and Jack Henningfield; as well as Peter Hendricks, an associate professor of psychiatry at the University of Alabama at Birmingham’s School of Public Health.

A resurgence of interest in psychedelics as medicine

Over the past several years, a handful of studies have suggested that psychedelic drugs like psilocybin could help treat a range of mental illnesses, including anxiety, depression, drug addiction, and PTSD.

One of those studies — a clinical trial published in the Journal of Psychopharmacology in 2016 — was written by Griffiths and Johnson, two authors of the recent piece outlining why psilocybin should be made medically available. Griffiths’ and Johnson’s seminal work concluded that in people with a terminal cancer diagnosis, a single high dose of psilocybin appeared to help pull them out of severe depression and anxiety. On a press call after the study came out, Griffiths likened the treatment to “a surgical intervention” for the mental illnesses.

Since then, research into drugs like LSD, ecstasy, ketamine, and marijuana (which many experts consider to have psychedelic properties) has abounded. Last year, a study suggested that ecstasy could help veterans cope with PTSD symptoms. Another recent paper hinted that ketamine could be used to curb severe depression. Several more recent studies of psilocybin have suggested it might help treat obsessive-compulsive disorder as well.

“At this point, the data suggest that the potential therapeutic benefits of psilocybin-assisted therapy are real, and of potential medical and public health significance,” the four authors wrote in their recent article.

The findings on psychedelics are also garnering the attention of investors and tech moguls. Just last month, German entrepreneur Christian Angermeyer launched a new biotech company called Atai with the mission of backing more psychedelic mental health research. Compass Pathways, a research startup studying and producing psilocybin for depression, recently attracted backing from tech magnate Peter Thiel.

But the legal classifications of these drugs not be keeping adequate pace with the research or the investments.

‘Replacing fear and misinformation with scientifically based facts’

Despite the ongoing research, neither the Food and Drug Administration nor the DEA has announced an intent to reschedule psilocybin or any other psychedelic. But such a move could happen. It did recently with marijuana.

In June, the FDA approved the first medicine made with a compound from cannabis. Called Epidiolex, the drug treats two rare forms of epilepsy using CBD, a marijuana compound that’s not responsible for a high. As a result of the FDA’s green light, the DEA was forced to reclassify CBD.

“We don’t have a choice on that,” DEA public affairs officer Barbara Carreno told Business Insider in June. “It absolutely has to become Schedule 2, 3, 4, or 5.”

So this September, the DEA officially shifted its stance on marijuana for the first time in 46 years by putting CBD in Schedule 5 alongside substances like cough syrup and sleep aids — all drugs that the agency considers at the lowest risk of abuse or harm.

In their article on psilocybin, the authors write that it too should be placed in Schedule 5, pending its approval as a medicine. Some experts say that could happen as soon as 2027.

“Schedule I is for substances with a high potential for abuse, lack of therapeutic approval, and that cannot be used safely in medicine,” they write. “History of use and available scientific data show that the first criterion is questionable, and the third criterion is likely not true.”

Meanwhile, the research on psilocybin is continuing to blossom. Clinical trial results from Compass are expected before 2020; researchers at the University of California, San Francisco are currently enrolling patients in a study to see whether psilocybin could assist in group therapy to improve the mental health of long-term AIDS survivors; and scientists at New York University aim to study whether psilocybin could be used to treat alcoholism.

Johnson, Griffiths, Henningfield, and Hendricks seem to believe the future of those studies — and psilocybin’s potential — is bright.

“This area of regulatory science has the potential to facilitate innovative therapeutic breakthroughs by replacing fear and misinformation with scientifically based conclusions and facts,” they wrote.

Read more of our psychedelic medicine coverage:

Drug danger chart shows which drugs you should never mix, and which you totally should

Vices September 10, 2018 By Eleanor Gray

Nobody is perfectly healthy. We all need drugs. Sometimes a combination of drugs. We get them from drug dealers.

Your indoor drug dealers — the ones who wear white lab coats, take payment by insurance, and operate under florescent lights — know about drug combinations: which drug combos are synergistic and heighten each other’s effects, which combinations you gotta be careful with. And which can kill you. They have apps and charts and books on it.

Your outdoor drug dealers, the ones who wear tie-dye shirts, take payment in beer, and operate under overpasses, don’t got jack. They’ll tell you that dilaudid and Benadryl will send you flying, or molly and caffeine is deadly, or Budweiser and vicodin makes Calculus II tolerable. This is how people aspirate and croak.

Well, the outdoor drug dealers are catching up in knowledge.

Read this amazing chart. It has twenty-five of the most popular scheduled drugs listed. Your safer drugs, like LSD, mushrooms and DMT, are on the top and left, and your more dangerous drugs, like opioids and benzos, are on the bottom and right.

Trace the columns and rows to find information on how safe, when combined, the drugs are. That’s 600 different interactions.

In the upper right corner of this chart is the key. Yellow squares warrant caution. Orange squares mean the combination is unsafe. Red squares mean it’s downright dangerous.

For example, mixing cocaine with alcohol is unsafe. Mixing opioids with benzos (for example, heroin with klonopin) is dangerous.

To see what, exactly, the negative effects can be, check out the individual drug entries on TripSit. They made the chart. A few other organizations, like DanceSafe can help you figure out what’s really in your molly and which drug combos are dangerous.

But this chart has a fascinating twist. Your DARE officer is going to hate this, but this chart doesn’t just show you what’s dangerous — it shows you what might be awesome.

The dark green squares show which drugs combination boost each other, while also being low-risk. These are “synergistic” combinations, i.e., heightening, while still posing a low risk to your physical health.

It’s mostly the natural, hippie drugs, like DMT and mushrooms, that are low-risk, and low-risk when combined. So LSD plus MDMA (“candyflipping”)- for example, is a music festival highlight, and listed here as “synergistic and low-risk.”

Low risk means physical low risk. High doses in the wrong situations, of course — like with strangers, or in public, in jail or on a bicycle — can wreck your head and ruin lives.

But there are 145 drug combinations listed as synergist and low-risk. That’s 145 fascinating and illuminating and relatively safe ways to flunk out of school. One hundred forty five psychologically traumatizing ways to pass a 10-hour workplace seminar.

And, maybe, 145 astonishing ways to change your life.

That’s because some of these combinations are known to be more than just excellent fun. For example, as the chart shows, when you take an antidepressant called an MAOI and ingest the natural psychedelic DMT, it’s not only synergistic and low risk, it’s called ayahuasca, and it can cure depression, drug addiction and acedia.

This chart has another interesting feature. It shows which drug combinations are merely boring. The light green squares show which combos are low risk but don’t add anything to the other. And the blue squares show drug combos are also low risk, but where each effects blunt the other. So alcohol, despite its wide use, actually dampens the effects of things like mushrooms or mescaline.

Caveat tripper, of course. This chart is mostly crowdsourced; it’s based on what trippers say happened to them; there aren’t many placebo-controlled, double-blind scientific studies here. Actual results may melt your face.

Also, the chart is extremely limited. It doesn’t show most legal drugs, which can be more dangerous than the illegal drugs. Talk to your doctor. (Seriously. Talk to her. She won’t snitch. Mine is extremely cool about this stuff.) And combine all this with the deep resources of Erowid, reddit and Wikipedia. And, please, please, please think real hard before you drink ayahuasca by yourself, or candyflip during a job interview, or hippieflip at the edge of the Grand Canyon.

But marvel at this chart as another amazing thing the Internet has brought us. It’s more proof that outdoor drug dealers can be nearly as responsible as the indoor drug dealers. And it’s more proof that regular drug users are doing work the government tried and failed to do, by showing which drugs, and drug combinations, are actually dangerous and can hurt us, and which drugs, and drug combinations, might actually help people live meaningful, enjoyable and purpose-driven lives.

Go to Article Roster – Click Here

Canadian Researchers: Use Medical Marijuana Instead Of Opioids

Using opiods for pain is a hard thing for many people.

Sure, the painkillers provide temporary relief from pain, but the side effects can be horrific. They tear up your organs, and often times lead to a level of addiction that ruins lives. If only there was another medicine out there that was effective that didn’t come with all of the problems…You see where I’m going with this. Medical marijuana is a proven form of treatment for pain, specifically neuropathic pain.

Recently researchers in Canada started pushing for Canadian doctors to substitute opioid based painkillers for medical marijuana. Per The Globe and Mail:

Canadian doctors should use medical marijuana instead of frequently abused opioids to treat patients with neuropathic pain and a host of other conditions cannabis has been proven to combat, Vancouver-based HIV/AIDS researchers argue in a newly published editorial.

Thomas Kerr, Julio Montaner and Stephanie Lake of the B.C. Centre for Excellence in HIV/AIDS argue the Canadian Medical Association is holding pot to a higher standard than other pain-relieving pharmaceutical drugs and is ignoring high-quality, peer-reviewed studies on the use of cannabis. Their editorial is in the latest edition of the Journal of the Canadian Public Health Association.

Dr. Kerr, co-director of the centre’s Urban Health Research Initiative, said five recent randomized control trials and two systemic reviews have found marijuana helps relieve neuropathic pain. Yet many doctors are still loathe to prescribe a drug that has not been approved by Health Canada.

Doctors should want their patients to get better, and in the meantime reduce their suffering. Getting patients hooked on pharmaceutical painkillers may reduce their suffering for a brief time, but it rarely results in patients getting better. As I said earlier, it often times ruins the person’s life with addiction and the creation of other ailments due to the side effects of the painkillers. Marijuana is medicine, proven by science, and it’s a much, much better alternative to pharmaceutical painkillers. It’s time that doctors in Canada, and around the world, got on board. People’s lives are depending on it.

See Story in – The Globe and Mail

IACM: Nomination of IACM Ambassadors

In order to establish a wider network that will work together toward its aims as mentioned in the statutes, the IACM has nominated ambassadors in different countries around the world. There are both Professional Ambassadors and Patient Ambassadors, as well as Partner Organizations

The list of ambassadors is as follows:

Professional Ambassadors
Alex Mabou Tagne (Cameroon)
Daniela Parolaro (Italy)
Donald Abrams (USA)
Ethan Russo (USA)
Francesco Crestani (Italy)
Franjo Grotenhermen (Germany)
Gastone Zanette (Italy)
Gianpaolo Grassi (Italy)
Ilya Reznik (Israel)
Kirsten Müller-Vahl (Germany)
Manuel Guzman (Spain)
Mark Ware (Canada)
Marlon Germon (South Africa)
Marry Lynn Mathre (USA)
Natalie Krapivensky (Australia)
Raquel Peyraube (Uruguay)
Roger Pertwee (UK)
Rudolf Brenneisen (Switzerland)
Steve Goldner (USA)

Patient Ambassadors
Alison Myrden (Canada)
Carola Pérez Gómez (Spain)
Hana Vágnerová (Czech Republic)
Marian Hutten (Netherlands)
Max Plenert (Germany)
Michael Krawitz (USA)
Sarah Martin (UK)
Sébastien Béguerie (France)

For more details about the ambassadorship program, you may contact our Partnership and Network Coordinator Yuval Zolotov at network@cannabis-med.org

Science/Human: Legalization of cannabis for medical use in the US is associated with reduced opioid prescriptions

“Statewide medical cannabis legalization appears to have been associated with reductions in both prescriptions and dosages of Schedule III (but not Schedule II) opioids received by Medicaid enrollees in the US,” scientists from the Department of Family Medicine and Public Health of the University of California in San Diego, USA, wrote. They analysed state-level opioid prescription records from 1993 to 2014 of data from Medicaid. Medicaid is a program that helps with medical costs for some people with limited income and resources.

For Schedule III opioid prescriptions, medical cannabis legalization was associated with a 29.6% reduction in number of prescriptions, 29.9% reduction in dosage, and 28.8% reduction in related Medicaid spending. No evidence was found to support the associations between medical cannabis legalization and Schedule II opioid prescriptions Authors estimated that, if “all the states had legalized medical cannabis by 2014, Medicaid annual spending on opioid prescriptions would be reduced by 17.8 million dollars.” Schedule II opioids are morphine, fentanyl and others. Schedule III opioids are buprenorphine, tramadol and others.

Liang D, Bao Y, Wallace M, Grant I, Shi Y. Medical Cannabis Legalization and Opioid Prescriptions: Evidence on US Medicaid Enrollees during 1993-2014. Addiction. 2018 Jul 10. [in press]

Science/Human: Cannabis use is associated with decreased mortality in hospital after a heart attack

In a study with 1,273,897 patients with acute myocardial infarctions cannabis use was associated with decreased in-hospital deaths. Furthermore, cannabis use was not associated with increased risk of adverse short-term outcomes following a heart attack. In total 3854 patients reported cannabis use. Researchers of the Division of Cardiology of the University of Colorado Anschutz in Aurora, USA, analysed hospital records from 8 states between 1994 and 2013.

Cannabis users were more likely to be placed on mechanical ventilation (odds ratio 1.19). They were significantly less likely to die (OR 0.79), experience shock (OR 0.74) or require an intra-aortic balloon pump (OR 0.80) after acute myocardial infraction (AMI) than patients with no reported cannabis use. Authors wrote that these “results suggest that, contrary to our hypothesis, marijuana use was not associated with increased risk of adverse short-term outcomes following AMI. Furthermore, marijuana use was associated with decreased in-hospital mortality post-AMI.”

Johnson-Sasso CP, Tompkins C, Kao DP, Walker LA. Marijuana use and short-term outcomes in patients hospitalized for acute myocardial infarction. PLoS One. 2018;13(7):e0199705.

Science/Human: CBD reduces seizures in several further childhood-onset epilepsy forms according to an open-label study

In an open study with 46 patients with CDKL5 deficiency disorder or Aicardi, Doose, and Dup15q syndromes a treatment with CBD reduced the frequency of convulsive seizures. Investigators of New York University School of Medicine, USA, included patients aged 1-30 years with these severe childhood-onset epilepsy forms. They were treated with CBD for at least 10 weeks.

The percent change in median convulsive seizure frequency for all patients taking CBD decreased from baseline to week 12 by 51.4% and week 48 by 59.1%. CBD was generally well tolerated. Authors wrote that the study “provides class III evidence for the long-term safety and efficacy of CBD administration in patients with treatment-resistant epilepsy” associated with these disorders.

Devinsky O, Verducci C, Thiele EA, Laux LC, Patel AD, Filloux F, Szaflarski JP, Wilfong A, Clark GD, Park YD, Seltzer LE, Bebin EM, Flamini R, Wechsler RT, Friedman D. Open-label use of highly purified CBD (Epidiolex®) in patients with CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes. Epilepsy Behav. 2018 Jul 10. [in press]

News in brief

Lebanon: Parliament considers cultivation of cannabis for medical use
Lebanon’s parliament is considering legalizing the cultivation of cannabis for medical purposes, Parliament Speaker Nabih Berri said on 18 July. Although growing the plant is illegal in Lebanon, landowners nevertheless have for decades openly grown cannabis in the fertile Bekaa Valley.
Reuters of 18 July 2018

Science/Human: Legalisation of cannabis in some US states is associated with improvement in some clearance rates by the police
Scientists assessed crime clearance rates in Colorado and Washington before and after the enactment of cannabis legalization for recreational use. Their findings suggest no negative effects of legalization on crime clearance rates. “Our findings suggest legalization has resulted in improvements in some clearance rates,” they wrote.
Department of Criminal Justice and Criminology, Washington State University, Pullman, USA.
Makin DA, et al. Police Quarterly. 2018 Jul 4. [in press]

Science/Animal: Endocannabinoids produced from omega-3 fatty acids have anti-cancer effects
The intake of omega-3 fatty acids increased the production of endocannabinoid substances (DHEA, EDP-EA) with anti-cancer effects in osteosarcoma, a bone cancer, by several mechanisms, including reduction of tumour growth, metastasis and the production of new blood vessels in the tumour. These effects were partially mediated through the cannabis receptor 1.
University of Illinois, Urbana, USA.
Science Daily of 13 July 2018
Roy J, et al. J Med Chem. 2018;61(13):5569-5579.

Science/Human: Large variation of plasma concentrations of THC and CBD after oral intake
In a study with 12 multiple sclerosis patients, who received 2 sprays of the cannabis extract Sativex containing 2.7 mg THC and 2.5 mg CBD in 1 spray, maximum concentrations in blood plasma varied considerably. Maximum THC plasma levels varied from 0.60 to 13.29 ng/mL and CBD plasma levels range from 0.55 to 11.93 ng/mL. Time to peak plasma concentrations ranged from 150 to 240 minutes for THC and 90 to 240 minutes for CBD.
IRCCS, Institute of Neurological Sciences, Bologna, Italy.
Contin M, et al. Clin Neuropharmacol. 2018 Jul 18. [in press]

Science/Cells: CBD may be effective in several breast cancer types
CBD induces apoptosis (programmed cell death) in several breast cancer cells, including ER -positive and triple negative breast cancer cells.
Department of Biochemistry, Faculty of Science, Alexandria University, Egypt.
Sultan AS, et al. 2018;41:34-41.

Science/Human: CBD was effective in several epilepsy forms in the long-term
In a long-term observational study with 607 patients treated at 25 sites in the US with CBD up to a maximum dose of 25 to 50 mg/kg bodyweight treatment effects after 96 weeks were similar to those after 12 weeks.
University of Alabama, Birmingham, USA.
Szaflarski JP, et al. Epilepsia. 2018 Jul 12. [in press]

Science/Human: The effect of cannabis on insomnia depended on the cannabis variety
In a study with 409 people with a specified condition of insomnia CBD was associated with greater symptom relief than THC. Flowers from sativa subtypes were associated with more negative side-effects than flowers from indica or hybrid plant subtypes.
Department of Psychology, University of New Mexico, Albuquerque, USA.
Vigil JM, et al. Medicines (Basel). 2018;5(3).

Science/Human: Pain patients who use cannabis have greater pain severity than non-users
According to a survey with 1514 pain patients contacted by phone cannabis use was associated with a greater pain severity score compared to non-users. Authors wrote that there “was no evidence that cannabis use reduced pain severity or interference or exerted an opioid-sparing effect.” However, it may also be possible, that patients with more severe pain are more likely to use cannabis.
National Drug and Alcohol Research Centre, Sydney, Australia.
Campbell G, et al. Lancet Public Health. 2018;3(7):e341-e350.

Science/Cells: Cannabis compounds interact synergistically for anti-cancer activity against colon cancer
Colon cancer cells were exposed to several ethanol extracts from cannabis. Researchers found that some cannabis compounds acted synergistically to produce toxic effects on these cancer cells, induce cell cycle arrest and apoptosis (programmed cell death). Among these compounds is cannabigerolic acid.
Agricultural Research Organization, Volcani Center, Bet Dagan, Israel.
Nallathambi R, et al. Cannabis Cannabinoid Res. 2018;3(1):120-135.

Science/Animal: A mechanism of action of CBD’s antidepressant effects
Researchers investigated the effects of CBD on a certain brain region (hippocampus) of mice. They wrote that the investigation suggests “that the hippocampal BDNF-TrkB-mTOR pathway is vital for cannabidiol-induced antidepressant-like effect.”
Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Brazil.
Sartim AG, et al. J Psychopharmacol. 2018:269881118784877.

Science/Human: Cannabis may have therapeutic effects in patients with sickle cell disease
An analysis of 44 patients, who received cannabis for medical reasons, showed that cannabis products may be beneficial in this patient group.
Yale Cancer Center, Yale University, New Haven, USA.
Roberts JD, et al. Cannabis Cannabinoid Res. 2018;3(1):162-165.

Science/Human: CBD is mostly used against pain, sleep disorders, anxiety and depression
In an online survey with 2409 participants recruited through social media almost 62% of CBD users reported using the cannabinoid to treat a medical condition. The top medical conditions were pain, sleep disorders, anxiety, and depression. Almost 36% of respondents reported that CBD treats their medical condition “very well.”
The Center for Medical Cannabis Education, Del Mar, USA.
Corroon J and Phillips JA.Cannabis Cannabinoid Res. 2018;3(1):152-161.

Science/Human: Cannabis users need higher doses of opioids after surgery
In an analysis of 434 patients, who underwent weight reduction surgeries, those with cannabis use (36 patients) need higher doses of opioids. Authors assume that this is due to the development of cross tolerance.
Saint Joseph Hospital, Denver, USA.
Bauer FL, et al. Perm J. 2018;22.

Science/Cells: Cannabigerol has anti-inflammatory and neuroprotective properties
The plant cannabinoid cannabigerol (CBG) protected nerve cells against the toxicity induced by stimulated macrophages. It counteracted the production of pro-inflammatory messengers.
IRCCS Centro Neurolesi “Bonino Pulejo”, Messina, Italy.
Gugliandolo A, et al. J Mol Sci. 2018;19(7).

Science/Animal: Activation of the peripheral CB1 receptor may be beneficial in chemotherapy-induced peripheral neuropathy
In a study with rats with cisplatin-induced peripheral neuropathy the administration of a synthetic cannabinoid, which does not penetrate into the brain, suppressed allodynia. Allodynia refers to a pain sensation from a stimulus (e.g. touch, cold), which usually does not cause pain.
Laboratory of Neuropharmacology, University of California, Los Angeles, USA.
Mulpuri Y, et al. Neuropharmacology. 2018;139:85-97.

Science/Cells: Activation of the CB2 receptor decreases viability of leukaemia cells
A new synthetic cannabinoid with high affinity to the CB2 receptor inhibits cell survival in leukaemia cells, but it did not damage normal healthy lymphocytes.
Department of Experimental Medicine, University of Rome “La Sapienza”, Italy.
Capozzi A, et al. Int J Mol Sci. 2018;19(7).

A glimpse @ the past

One year ago

Horizontal gene cluster transfer increased hallucinogenic mushroom diversity

– Reynolds – 2018 – Evolution Letters – Wiley Online Library

Secondary metabolites are a heterogeneous class of chemicals that often mediate interactions between species. The tryptophan‐derived secondary metabolite, psilocin, is a serotonin receptor agonist that induces altered states of consciousness. A phylogenetically disjunct group of mushroom‐forming fungi in the Agaricales produce the psilocin prodrug, psilocybin. Spotty phylogenetic distributions of fungal compounds are sometimes explained by horizontal transfer of metabolic gene clusters among unrelated fungi with overlapping niches. We report the discovery of a psilocybin gene cluster in three hallucinogenic mushroom genomes, and evidence for its horizontal transfer between fungal lineages. Patterns of gene distribution and transmission suggest that synthesis of psilocybin may have provided a fitness advantage in the dung and late wood‐decay fungal niches, which may serve as reservoirs of fungal indole‐based metabolites that alter behavior of mycophagous and wood‐eating invertebrates. These hallucinogenic mushroom genomes will serve as models in neurochemical ecology, advancing the (bio)prospecting and synthetic biology of novel neuropharmaceuticals.

See Story here – Wiley Online Library

Psychedelics Promote Structural and Functional Neural Plasticity

Neuropsychiatric diseases, including mood and anxiety disorders, are some of the leading causes of disability worldwide and place an enormous economic burden on society (Gustavsson et al., 2011, Whiteford et al., 2013). Approximately one-third of patients will not respond to current antidepressant drugs, and those who do will usually require at least 2–4 weeks of treatment before they experience any beneficial effects (Rush et al., 2006). Depression, post-traumatic stress disorder (PTSD), and addiction share common neural circuitry (Arnsten, 2009, Russo et al., 2009, Peters et al., 2010, Russo and Nestler, 2013) and have high comorbidity (Kelly and Daley, 2013). A preponderance of evidence from a combination of human imaging, postmortem studies, and animal models suggests that atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiology of depression and related disorders and is precipitated and/or exacerbated by stress (Arnsten, 2009, Autry and Monteggia, 2012, Christoffel et al., 2011, Duman and Aghajanian, 2012, Duman et al., 2016, Izquierdo et al., 2006, Pittenger and Duman, 2008, Qiao et al., 2016, Russo and Nestler, 2013). These structural changes, such as the retraction of neurites, loss of dendritic spines, and elimination of synapses, can potentially be counteracted by compounds capable of promoting structural and functional neural plasticity in the PFC (Castrén and Antila, 2017, Cramer et al., 2011, Duman, 2002, Hayley and Litteljohn, 2013, Kolb and Muhammad, 2014, Krystal et al., 2009, Mathew et al., 2008), providing a general solution to treating all of these related diseases. However, only a relatively small number of compounds capable of promoting plasticity in the PFC have been identified so far, each with significant drawbacks (Castrén and Antila, 2017). Of these, the dissociative anesthetic ketamine has shown the most promise, revitalizing the field of molecular psychiatry in recent years.

Ketamine has demonstrated remarkable clinical potential as a fast-acting antidepressant (Berman et al., 2000, Ionescu et al., 2016, Zarate et al., 2012), even exhibiting efficacy in treatment-resistant populations (DiazGranados et al., 2010, Murrough et al., 2013, Zarate et al., 2006). Additionally, it has shown promise for treating PTSD (Feder et al., 2014) and heroin addiction (Krupitsky et al., 2002). Animal models suggest that its therapeutic effects stem from its ability to promote the growth of dendritic spines, increase the synthesis of synaptic proteins, and strengthen synaptic responses (Autry et al., 2011, Browne and Lucki, 2013, Li et al., 2010).

Like ketamine, serotonergic psychedelics and entactogens have demonstrated rapid and long-lasting antidepressant and anxiolytic effects in the clinic after a single dose (Bouso et al., 2008, Carhart-Harris and Goodwin, 2017, Grob et al., 2011, Mithoefer et al., 2013, Mithoefer et al., 2016, Nichols et al., 2017, Sanches et al., 2016, Osório et al., 2015), including in treatment-resistant populations (Carhart-Harris et al., 2016, Carhart-Harris et al., 2017, Mithoefer et al., 2011, Oehen et al., 2013, Rucker et al., 2016). In fact, there have been numerous clinical trials in the past 30 years examining the therapeutic effects of these drugs (Dos Santos et al., 2016), with 3,4-methylenedioxymethamphetamine (MDMA) recently receiving the “breakthrough therapy” designation by the Food and Drug Administration for treating PTSD. Furthermore, classical psychedelics and entactogens produce antidepressant and anxiolytic responses in rodent behavioral tests, such as the forced swim test (Cameron et al., 2018) and fear extinction learning (Cameron et al., 2018, Catlow et al., 2013, Young et al., 2015), paradigms for which ketamine has also been shown to be effective (Autry et al., 2011, Girgenti et al., 2017, Li et al., 2010). Despite the promising antidepressant, anxiolytic, and anti-addictive properties of serotonergic psychedelics, their therapeutic mechanism of action remains poorly understood, and concerns about safety have severely limited their clinical usefulness.

Because of the similarities between classical serotonergic psychedelics and ketamine in both preclinical models and clinical studies, we reasoned that their therapeutic effects might result from a shared ability to promote structural and functional neural plasticity in cortical neurons. Here, we report that serotonergic psychedelics and entactogens from a variety of chemical classes (e.g., amphetamine, tryptamine, and ergoline) display plasticity-promoting properties comparable to or greater than ketamine. Like ketamine, these compounds stimulate structural plasticity by activating the mammalian target of rapamycin (mTOR). To classify the growing number of compounds capable of rapidly promoting induced plasticity (Castrén and Antila, 2017), we introduce the term “psychoplastogen,” from the Greek roots psych- (mind), -plast (molded), and -gen (producing). Our work strengthens the growing body of literature indicating that psychoplastogens capable of promoting plasticity in the PFC might have value as fast-acting antidepressants and anxiolytics with efficacy in treatment-resistant populations and suggests that it may be possible to use classical psychedelics as lead structures for identifying safer alternatives.

Because atrophy of cortical neurons is believed to be a contributing factor to the development of mood and anxiety disorders (Christoffel et al., 2011, Duman and Aghajanian, 2012), we first treated cultured cortical neurons with psychedelics from a variety of structural classes (Figures 1A and S1A) and measured the resulting changes in various morphological features. Using Sholl analysis (Ristanović et al., 2006), we observed that several psychedelics increased dendritic arbor complexity comparably to ketamine, as measured by the area under the curve of the Sholl plots as well as the maximum number of crossings (Figures 1B–1E and S1B–S1E). This increase in arbor complexity appeared to result from large changes in both the number of dendritic branches and the total length of the arbors (Figures 1F, 1H, S1F, and S1H). Psychedelics had a limited effect on the number of primary dendrites and did not alter the length of the longest dendrite (Figures 1G, 1I, S1G, and S1I).

Nearly all psychedelic compounds tested were capable of robustly promoting neuritogenesis, with comparable effects being produced by tryptamines (N,N-dimethyltryptamine [DMT] and psilocin), amphetamines (2,5-dimethoxy-4-iodoamphetamine [DOI] and MDMA), and ergolines (lysergic acid diethylamide [LSD]). As a positive control, we treated cells with 7,8-dihydroxyflavone (DHF), a psychoplastogen structurally dissimilar to classical psychedelics (Jang et al., 2010), and found that it also increased dendritic arbor complexity (Figure S2). This neurite outgrowth structural phenotype seems to only be induced by select compounds because serotonin and D-amphetamine, molecules that are chemically related to classical psychedelics and entactogens, exerted minimal to no effects on neuritogenesis (Figure S2).

To establish the relative potencies and efficacies of hallucinogens and entactogens for promoting neurite outgrowth, we conducted 8-point dose-response studies (Figure S3). We defined 100% and 0% efficacy as the maximum number of crossings induced by ketamine (10 μM) and vehicle (0.1% DMSO), respectively. We chose the 10 μM concentration of ketamine as the upper limit because this concentration of ketamine is reached in the brain following intraperitoneal administration of an antidepressant dose in rats (Yang et al., 2018). For consistency, we used this same concentration when testing the effects of psychedelics and entactogens, with DMT being the only exception. We used a maximum 90 μM concentration of DMT in our studies to more closely mimic the brain concentration of DMT in rats treated with an antidepressant dose (Cohen and Vogel, 1972, Cameron et al., 2018). In this neuritogenesis assay, ketamine’s half maximal effective concentration (EC50) value was 132 nM. Surprisingly, the majority of the psychedelics and entactogens we tested exhibited significantly greater potency than ketamine, with LSD being particularly potent (EC50 = 0.409 nM). In fact, LSD exhibited activity across 8 orders of magnitude into the low picomolar range (Figure S3).

Notably, the anti-addictive alkaloid ibogaine (Alper, 2001, Belgers et al., 2016) was the only psychedelic tested that had absolutely no effect (Figure S4). This was a surprising result because we hypothesized that ibogaine’s long-lasting anti-addictive properties might result from its psychoplastogenic properties. Previous work by He et al. (2005) clearly demonstrated that ibogaine increases the expression of glial cell line-derived neurotrophic factor (GDNF) and that this plasticity-promoting protein is critical to ibogaine’s anti-addictive mechanism of action. Because several reports have suggested that noribogaine, a metabolite of ibogaine, might actually be the active compound in vivo (Zubaran et al., 1999, Baumann et al., 2000, Baumann et al., 2001), we decided to test its ability to promote neuritogenesis in cultured cortical neurons. Gratifyingly, noribogaine robustly increased dendritic arbor complexity with an EC50 value comparable to ketamine (Figure S3), providing additional evidence suggesting that it may be the active compound in vivo.

To assess the in vivo effects of classical psychedelics on neuritogenesis, we started treating Drosophila larvae during the first instar with LSD and DOI. As observed in rodent cortical cultures, both LSD and DOI significantly increased dendritic branching of class I sensory neurons; however, they did not increase the total length of the dendritic arbors (Figures 1J–1L). Because of the striking effects of psychedelics on the structures of immature neurons, we hypothesized that they might influence neurodevelopment. To test this, we chronically treated zebrafish embryos with compounds for 6 days immediately following dechorionation and assessed gross morphological changes and behavior. We did not observe any differences in head sizes between the treatment groups, nor did we detect any statistically significant differences in activity levels (Figure S5). Next we assessed the ability of psychedelics to promote neuritogenesis in more mature neurons by starting to treat Drosophila larvae during the late second instar. Again, psychedelics increased the branching of class I neurons, although the effect was less dramatic than that observed when treatment was started during the first instar (Figure 1M–1O). Although different developmental stages might be more or less susceptible to the effects of psychedelics, it is also possible that the smaller effect size observed after administering compounds starting at the later time point was simply the result of treating the larvae for a shorter period of time. Regardless, it was quite surprising to observe compound-induced changes in neuronal structure after initiating treatment during the late second instar because class I neurons are stereotyped and typically possess relatively few higher-order branches (Grueber et al., 2002). Moreover, our results demonstrate that psychedelics can promote changes in neuronal structure across vertebrate (rats) and invertebrate (Drosophila) species, suggesting that they act through an evolutionarily conserved mechanism.

Information can be found here – Psychedelics Promote Structural and Functional Neural Plasticity

Research on psychedelics makes a comeback

Forty years after federal laws criminalized the use of psychedelics for non-medical purposes in FDA-regulated psychological and drug research, the study of these drugs is picking up again, and their use in treating certain patients shows promise. Researchers are finding that the drugs may help improve functioning and lift the spirits of those with cancer and other terminal diseases, as well help treat people with post-traumatic stress disorder.

In a pilot study published online in September and slated to appear in the January 2011 Archives of General Psychiatry (Vol. 68, No. 1), University of California, Los Angeles, researchers led by Charles Grob, MD, showed that a modest dose of psilocybin — the active ingredient in “magic mushrooms” — given to terminal cancer patients under the supervision of trained therapists helped ease anxiety and improve mood for up to six months. In addition to feeling calmer and happier, researchers say, the participants reported forging a closer connection to friends and family members.

These types of research studies have continued to point to the possibility that the benefits of these illegal drugs may outweigh the risks in certain scenarios. As a result, the FDA and the Drug Enforcement Administration have eased regulations and also given approval to researchers at Johns Hopkins University and New York University’s Langone Medical Center to study the use of psilocybin to treat death anxiety among cancer patients.

Several other small-scale studies have also shown success in using another mind-altering drug — MDMA, often referred to as ecstasy — in conjunction with psychotherapy to treat PTSD. In a study with 20 patients published online in July in the Journal of Psychopharmacology, South Carolina-based psychiatrist Michael Mithoefer, MD, and colleagues provided two eight-hour psychotherapy sessions to patients, half of whom received a dose of MDMA during the sessions and the other half a placebo. Two months after the last session, researchers found that more than 80 percent of the trial group no longer met diagnostic criteria for PTSD, compared with only 25 percent of the control group. Mithoefer is now recruiting subjects for a pilot study of PTSD treatment among veterans.

In all of these studies, the goal was to help patients reduce their fears, says Thomas Roberts, PhD, an educational psychologist at Northern Illinois University and co-editor of “Psychedelic Medicine” (Praeger, 2007). “It is more psychotherapeutic than biological or neurological,” he says.

It’s important to note, researchers say, that psychedelic drugs can elicit fear, anxiety or paranoia, depending on the dose provided and an individual’s personality. Therefore, this research is done only in a carefully controlled setting and under the care of a trained therapist.

Rick Doblin, PhD, executive director of the Multidisciplinary Association of Psychedelic Studies, a California-based nonprofit organization that is funding several of these studies, says psychologists will be increasingly tapped to conduct this research and explore the ramifications of the use of psychedelics.

“Considering how important improving end-of-life care has become in our society, as evidenced by the rise of the hospice movement, I think it’s likely that this field will continue to expand and become more relevant,” Doblin says.

—A. Novotney

Magic Mushrooms!

P.W. Barber is the author of Psychedelic Revolutionaries: LSD and the Birth of Hallucinogenic Research.

Somewhere, a Cheshire Cat is smiling.

If you’ve been paying attention to the health news of late, you might think you’ve have travelled back in time to the 1960s. It’s not a bad acid trip. We are in the midst of a “renaissance” in psychedelic science, as the author Michael Pollan called it last month in the pages of The New York Times. Researchers are examining the potential of drugs like LSD and psilocybin (“magic mushrooms”) – recreational drugs mostly associated with the 1960s counterculture – to act as psycho-therapeutic tools in the treatment of severe addictions, end-of-life anxiety, depression, and post-traumatic stress disorder. We’re high on getting high.

Truth be told, many of the new findings are in fact old discoveries from the 1950s and 60s – dusted off and updated for the 21st century. Uncovering this revolutionary past has much to offer to the movement that is presently unfolding in Canada and abroad.

When classic psychedelics, particularly lysergic acid diethylamide (LSD), were legally banned, and restrictions against their use put in place, in the late 1960s and 70s, the widely held opinion in the psychiatric and scientific communities – and, at least among non-users, society at large – was that they were too dangerous. Psychedelics, many argued, had the potential for serious abuse. Furthermore, claims of their medical value were overinflated and lacking a firm evidence base. Not surprisingly, this resulted in a halt to scientific research in the area – although recreational use continued.

Psychedelic science’s demise has become the subject of a growing body of historical analyses over the last decade, many of which point to, as contributing factors, a convoluted mixture of 1960s countercultural excesses (that is, psychedelic gurus and the LSD social movement), transformations in psychiatry (and how mental illnesses are understood, diagnosed and treated as well as what constitutes acceptable clinical research methodology), and even the covert experimentation of the U.S. Central Intelligence Agency (CIA).

After several decades of being in cryogenic stasis, experimental research with psychedelics is back and attracting the attention of those in and outside of the scientific community. Leading the charge is a new generation of researchers, based out of centres such as Johns Hopkins University, New York University and Britain’s Imperial College in London, whose findings hold promise in treating mental illness.

Attitudes toward recreational drugs are shifting in North America, with legalization of recreational marijuana increasingly prevalent in the United States, and, come Oct. 17, across Canada. Could magic mushrooms be next?

Perhaps no one definitive answer exists to answer the question of why we’re in the midst of this so-called renaissance in psychedelic science. Certainly, many have alluded to mental health and addictions systems being in crisis.

Gauging by the staggering human and financial costs associated with mental health and addictions, plus the fact that demand for services and treatment appear to be outpacing the supply, it is easy to see why there is concern.

Roughly one in five people in Canada experience a mental illness in their lifetime. According to CAMH, Canada’s premier research and treatment centre for mental health and addictions, 6.7 million Canadians suffer from mental illness, the cost of which is estimated to be $51-billion a year when factoring in health-care costs, lost productivity and reductions in health-related quality of life.

In the United States, recent data indicate that more than 43 million Americans suffer from a mental-health disorder and close to half of that number have a co-occurring substance-abuse disorder. Approximately 9.6 million Americans have been found to experience suicidal ideation. In terms of economic costs, the U.S. Substance Abuse and Mental Health Services Administration estimated the costs of mental illness to be a whopping US$467-billion in 2012.

In one area alone – that of PTSD among returning U.S. veterans of the Iraq and Afghanistan wars – the costs are alarming, with one in five veterans (300,000) diagnosed with the disorder. As revealed by some PTSD figures from the same year, first-year treatment cost the government US$8,300 a person, for a total of more than US$2-billion. To add to this, suicides among active-duty military personnel averaged one a day, 20 per cent of all suicides in the United States.

U.S. research has also revealed another troubling statistic: Americans with serious mental illnesses on average die 15 to 30 years earlier than those without, largely owing to the fact that the former have far higher rates of chronic diseases such as cancer, heart disease, stroke, diabetes and respiratory problems (interestingly, the study does not address what, if any, role the current medications used to treat severe mental illness may have had in contributing to these chronic diseases).

There’s no question: We need to do more – and better.

Drugs, of course, have come to occupy an ever growing role in mental-health systems. From the early years of the psychopharmacological revolution in the 1950s onward, we have seen a proliferation in the number of drugs used to treat psychiatric disorders, with numerous variations of anxiolytics, antidepressants, anti-psychotics and other psychotropic medications. Whether these drugs, and the theories that go with them, have been a help or hindrance in the battle against mental illness continues to be a source of heated debate.

In an interview with The Canadian Press earlier this year, University of Saskatchewan medical historian Erika Dyck speculated the revival of scientific interest in these taboo drugs might have to do with people’s desperation to find a therapy that works.

Most professionals working in the field will admit the standard medications being used to treat severe mental illnesses and addictions have their obvious benefits, but they also come with significant limitations; at best, the drugs have proven to be effective in the management of symptoms, and for some patients more than others. Unfortunately, the drugs have not been nearly as effective in treating the underlying illness.

In a recent episode of CBC Radio’s White Coat, Black Art, Brian Goldman profiles the burgeoning use of these drugs and just how difficult it is for some people to stop taking them. Citing data from a New York Times article, Dr. Goldman noted that from 2013 to 2014, 34.4 million adults were taking antidepressants, an increase of 250 per cent from a survey completed in 1999 to 2000. Canada also happens to be one of the largest consumers of antidepressants, ranking third on an Organization for Economic Co-operation and Development list of industrialized countries.

More problematic is the fact many of those taking antidepressants are long-term users who face the difficult challenge of withdrawal when attempting to discontinue the medications.

Along with psychopharmaceuticals such as anti-depressants, opioids are another burgeoning area of drug use – and abuse – in North America. Commonly used for pain management or to treat addictions, they are now associated primarily with a crisis that dominates today’s news headlines. Psychedelics may have a hand to play here as well. In the 1990s, Russian researchers Krupitsky et al. employed the Saskatchewan psychedelic therapeutic model, using “high dose” ketamine to successfully treat heroin addiction. And today, there continues to be discussion around the potential of other psychedelics (such as ibogaine and ayahuasca) to achieve lasting abstinence from opioid addiction, with some addicts turning to psychedelic therapy as an alternative to opiate replacement drugs such as methadone and suboxone.

In Canada, opioid-related overdoses now account for more deaths than automobile accidents; this week, the Special Advisory Committee on the Epidemic of Opioid Overdoses released data revealing that almost 4,000 Canadians died as a result of opioids last year – with over 90 per cent of these deaths being ruled as accidental or unintentional – a staggering 34 per cent increase from 2016. (One of the more disconcerting stories to have appeared in recent years has been how some pharmaceutical companies intentionally underplayed the highly addictive nature of their drugs so as to not interfere with marketing efforts and profits.)

Number of apparent opioid-related deaths in Canada by manner of death, 2016 and 2017

Accident (unintentional) – Suicide – Undetermined
How Accident (unintentional) Suicide Undetermined
2016 2624 258 96
2017 3671 173 143

Given these scenarios, it begs the question of whether adding psychedelics, whose safety and medical value are still contested, to the mix is a good idea. Granted, the notion that powerful mind-altering substances such as psilocybin might in some way help to alleviate the mental-health and addictions crisis might strike some as ridiculous, unethical or just plain scientifically unsound. Yet, we are once again at a point in time where which these drugs are receiving serious scientific consideration.

New developments on the medical and recreational cannabis front have definitely helped to open the door to other possibilities in psychedelic science. In Canada and many parts of the United States, we have taken an almost 180-degree turn from the era of “reefer madness” to today, when marijuana is being touted for its medical and other benefits.

A group of Canadian psychologists that recently carried out a literature review on medicinal and recreational cannabis pointed to the effectiveness of the drug in treating various ailments, most notably the symptoms related to PTSD. Interestingly, the review also reported on findings from American states where a rise in cannabis, used legally for harm reduction, has correlated with a decrease in opioid overdoses. And just a couple of weeks ago, this newspaper reported on national research that indicated people suffering from PTSD but not medicating with cannabis are far more at risk for depression and suicidal ideation than those who do use cannabis; also referenced were the country’s first randomized controlled trials to assess the usefulness of the drug in treating the disabling disorder.

In the foundational years of psychopharmacology, hallucinogenic drugs such as mescaline and LSD were an integral part of psychiatric research, initially for their ability to produce model psychoses in healthy subjects and then as adjuncts in the psychotherapeutic treatment of various mental ailments and substance-abuse disorders.

One of the more interesting, and one might argue revolutionary, case studies to emerge in the history of psychedelic science was that of Saskatchewan’s research program, which lasted from 1951 until 1961.

During the 1950s, the province was on the cutting edge of mental-health research. Its work with psychedelic drugs in particular spawned numerous theories and novel approaches to psychiatric treatment, creating a situation that led psychopharmacologist David Healy to remark that “Weyburn and Regina were almost as important lights in the psychopharmacological firmament as Paris and Basel.”

In the 1950s, Saskatchewan was one of the first places to conduct human experiments with LSD, assessing its physiological, biochemical and psychological effects and, in the process, mapping out the unknown territories of the “other world.” The Saskatchewan research, in fact, was responsible for the first, and perhaps only, Handbook on the Therapeutic Use of LSD; it fostered a radically innovative mental-hospital design based upon the drug experience; and yes, it will also go down in history for originating the term psychedelic (“mind manifesting”), which psychiatrist Humphry Osmond coined in 1956. Among the major highlights of the research, however, were the accomplishments in the areas of schizophrenia and alcoholism.

A 1958 story in The Globe and Mail notes Saskatchewan researchers’ efforts to treat alcoholism with LSD.

At a time when Freudian/psychoanalytical thought dominated psychiatry and theories surrounding schizophrenia, the Saskatchewan researchers, under the direction of the psychiatric duo of Dr. Osmond and Abram Hoffer, led the way in the turn toward biological psychiatry.

As with other researchers of hallucinogens in the 1950s, Saskatchewan’s psychedelic scientists were initially preoccupied with the psychotomimetic (“madness mimicking”) properties of the drugs and their ability to offer a glimpse into the worldview of patients with schizophrenia and other psychoses. But the province quickly separated itself from the rest of the pack in advancing the first specific biochemical theory for the disease (that is, the adrenalin metabolite hypothesis), which, in turn, led to a unique paradigm for understanding, diagnosing and treating the disease.

Based upon two key observations – that mescaline and adrenalin possessed uncanny structural similarities and that mescaline (and other hallucinogens) produced effects in healthy individuals nearly indistinguishable from symptoms associated with acute schizophrenia – Dr. Hoffer and Dr. Osmond launched a full-scale search for the “Mescaline-like Factor” in the human body, which they presumed to be a result of faulty adrenalin metabolism.

The researchers identified adrenochrome as one potential candidate, synthesizing the first pure samples of the chemical and proving it to possess psychotomimetic properties. Their next step was to begin experimenting with possible treatments that might prevent or cut down on the production of the hypothesized toxic substance. (Dr. Hoffer and Dr. Osmond’s use of massive doses of common vitamins such as niacin and ascorbic acid, and their claims of success in restoring wellness to many patients diagnosed with schizophrenia, became the subject of one of the, if not the biggest, controversies in post-Second World War psychiatry.)

Saskatchewan researchers were also among the first to use hallucinogens as therapeutics and as tools in understanding the human mind in general. With the assistance of psychologist Duncan Blewett, the team under Dr. Hoffer and Dr. Osmond became known for their explorations into the psychedelic applications of the drugs. One of their most noteworthy forays was the co-creation of psychedelic-assisted therapy for the treatment of alcoholism, wherein the drug was administered to patients with the goal of achieving a mystical conversion-type experience.

At its peak, Saskatchewan was one of the only places in the world to incorporate this type of therapeutic option as a standard approach to dealing with alcoholism. The positive outcomes achieved with what were described as “hopeless cases” turned heads, the likes of which included Alcoholics Anonymous co-founder Bill W. and High Priest Timothy Leary.

But the hype surrounding Saskatchewan’s psychedelic research was short-lived. By the time the research concluded in the early 1960s, it was embroiled in a series of controversies and would soon be faced with scientific findings from other research centres that failed to replicate its positive findings. At least this has been the standard narrative regarding this episode in psychedelic science history. A fuller reconstruction of the Saskatchewan story, however, makes for a much more complicated picture. It also reveals a host of myths and misconceptions that have lasted to this day, for example, that the research was inseparable from, and even promoted, LSD’s countercultural manifestations or that it was covertly sponsored by the CIA’s MKUltra program.

By 1970, LSD and other psychedelics had become anathema to mainstream scientific and medical communities, their contributions to psychiatric and psychopharmacological history “flushed down the memory hole.”

Despite psychedelics’ illustrious history and their future promise, not everyone is on board. In a recent article in Harper’s magazine, Nick Richardson takes issue with what he feels Michael Pollan and other surveyors of the renaissance to be saying, essentially that “the drugs are a net good and have been banned for nefarious reasons.” Mr. Richardson expresses discomfort with the idea of psychedelic drugs resulting in mystical experiences and is “wary of placing too much trust in psychedelic revelations.” Not only that, he finds psychedelic therapy “to be a little creepy.” I am sure he is not the only one who feels this way.

But Mr. Richardson tends to view pro-psychedelic statements such as those of Mr. Pollan in the same vein as those of psychedelic pied piper Dr. Leary because of their “believing the dangers of psychedelics to be almost non-existent.” I cannot say with absolute certainty that Mr. Pollan denies the dangers inherent in the use of psychedelics; most of the researchers he interviewed would have stressed the dangers involved in psychedelic pursuits, but that these dangers could be controlled for provided the appropriate “set and setting.”

The point here is that suggestions that psychedelics possess scientific and medical value should not be equated with a call for some psychedelic-fuelled utopia or with an appeal to the youth of the world to “turn on, tune in and drop out.” We have hopefully moved beyond the black-and-white portrayals of the drugs as either the panacea for all that ails humankind or the societal scourge they were made out to be at the height of the LSD mania in the 1960s.

Dr. Leary, who coined the phrase ‘turn on, tune in and drop out,’ became a 1960s counterculture icon for extolling the benefits of psychedelic drugs.

Today’s studies seem to indicate that there was validity to some of the earlier discredited research. Take psychedelic-assisted therapy for alcoholism as one example. In a 2012 meta-analysis of early randomized controlled experiments with LSD and alcoholism, Norwegian researchers Krebs and Johansen revealed that, in spite of methodological inconsistencies and weaknesses, “the effectiveness of a single dose of LSD compares well with the effectiveness of daily naltrexone, acamprosate or disulfiram,” three standard medications used to manage alcohol dependence.

The psychedelic renaissance is still in its early days and many challenges lie on the road ahead. Regulatory hurdles and funding still stand as the biggest barriers to present-day research, although government agencies responsible for the regulation and approval of drugs, such as the U.S. Food and Drug Administration and Health Canada, have displayed more openness to the possibility that psychedelics might afford a “breakthrough” with certain mental illnesses and addictions. As it currently stands, most psychedelic drugs continue to be classed under the most restrictive drug schedules for controlled substances, a decision that was made for mostly political reasons.

It is doubtful the support of the pharmaceutical industry will be forthcoming any time soon, which is not surprising given the fact psychedelics pose a direct threat to its bottom line. In the case of psychedelic-assisted therapy, the drugs are a component, albeit a very important component, of a carefully structured therapeutic matrix that has the potential to achieve results in one to two sessions. (Researchers have shown how a single exposure to psychedelics has produced immediate and lasting improvements in symptoms for the patient that last long after the drug has been metabolized and gone from the body.) For this reason alone, psychedelics would not be very appealing to pharmaceutical companies, whose profits depend on clients taking their products on a daily basis for months and years on end.

Many of the successful studies to date have managed to get around these barriers through the dedication and generous funding of non-profit organizations such as the Multidisciplinary Association for Psychedelic Studies (MAPS). One of the most advanced areas of study at this time remains the Phase 3 clinical trials unfolding in Canada, the United States and Israel using MDMA (“ecstasy”)-assisted therapy to treat cases of PTSD.

Further advancement in psychedelic science will depend on many things, but there is reason for optimism. If psychedelics are to find a place in mainstream medicine, progress must occur along a scientific path; it will not occur through some social or quasi-religious psychedelic movement, a fact best summed up in a statement by British psychiatrist Ben Sessa’s statement that “doctors need randomized, double-blind, placebo controlled clinical studies, not anecdotal drug experiences, no matter how convincing they may seem to the users.”

Time will tell if we are in store for a repeat performance of psychedelic science circa 1960s or if the field will advance sufficiently to the point where a new era is upon us.

Can anything – LSD perhaps? – help ‘suicide headaches?’

They’re known as “suicide headaches.” Patients claim the pain from cluster headaches is far worse than anything else human beings typically encounter, including childbirth and gallstones.

Bernard Greenberg, a 76-year-old retired cancer doctor from West Chester, has had “the most painful headaches imaginable” for 15 years. They make him feel as if he has “an ice pick going through my temple to my brain.”

Chris Hannah, 54, started having cluster headaches every day at 48. The Doylestown man describes his as feeling like a “severe electrical storm” with “erratic shards of pain” behind his left eye and from his ear to his jaw.

Yet these headaches have gotten surprisingly little research attention over the last 20 years. Their cause is unknown, and patients have had little choice but to try drugs meant for migraines or other conditions. Some patients have become so frustrated with their options that they have experimented with low doses of hallucinogenic mushrooms, which some claim are more effective than legal drugs.

“These people are in dire need of treatment,” said Stephen Silberstein, director of the Jefferson Headache Center.

William Ratner, a pharmacist who is senior marketing director for migraine and headache for Eli Lilly, said companies have had trouble coming up with good treatments.

“It’s not for lack of trying,” he said. “The science just hasn’t been there to help people in a major way.”

Patient groups have lobbied for more clinical trials of treatments specifically for cluster headaches, and that is finally happening. Local doctors are testing a new monoclonal antibody from Lilly and a wand that stimulates a key nerve through a small implant in a patient’s cheek. Doctors and patients are awaiting the Food and Drug Administration’s decision on another type of electrical stimulation that targets the vagus nerve. A trial that will for the first time scientifically test whether magic mushrooms really do help – no small feat in the risk-averse research world – may start soon.

The question of whether illegal psychedelic drugs can help headache patients has been “radioactive,” said Brian McGeeney, a Boston Medical Center neurologist who thinks the drugs deserve more study.

Sharp, one-sided pain

Cluster headaches are nothing like the tension headaches that almost everyone has experienced. Their intensity has more in common with migraines, but doctors say there are key differences. Migraines are sick headaches. Sufferers – there are more women than men – often feel nauseated and want to lie down in a dark room.

Cluster headaches have sharp, one-sided pain that leaves victims – there are more men than women – feeling “activated, like they want to run around the block or smack their head against the wall,” said John Detre, a Penn Medicine neurologist. Eyes often turn red and water. Noses run. Cluster headaches tend to be shorter than migraines, about 15 minutes to an hour.

They’re called cluster headaches because they tend to come in groups. Most sufferers have “episodic” headaches, or attacks that occur for two to three months out of a year, said William Young, a Jefferson headache specialist. About 20 percent of cluster sufferers have “chronic” headaches that happen every day like Hannah’s.

Estimates of how many people have cluster headaches vary considerably, but doctors say the condition affects about as many Americans as multiple sclerosis, around 400,000.

Patients are often treated with drugs in the triptan family, which can be injected under the skin or inhaled. Inhaling pure oxygen helps shorten some people’s attacks. Each of these helps about 70 percent of patients, said Jason Rosenberg, a headache specialist with Kaiser Permanente of the Mid-Atlantic States. Doctors often put patients in the midst of an attack on a course of high-dose steroids.

“Even the most proven treatments are suboptimal in terms of cost and convenience,” Rosenberg said.

Hannah, who founded the Cluster Headache Support Group in 2012, said he has up to eight headaches a day. Of the medicines available, he said, “I’ve tried them all, with varying levels of success.”

For the last 21/2 years, he’s been receiving infusions of the anesthetic drug ketamine at Jefferson. By far, he said, that has worked best, though he still has constant, “light” head pain. His doctor, Young, said he is collecting information about patients such as Hannah.

Magic mushrooms

Bob Wold, a Chicago-area man who has had cluster headaches for 38 years, started another support group, Clusterbusters, in 2002. He said he has tried 70 medications in myriad combinations with little relief. For the last 15 years, he has used something else that largely keeps the headaches at bay: magic mushrooms, or, presumably their active ingredient, psilocybin. He said four to six doses of mushrooms a year have let him stop all other medications for the last decade. He still uses oxygen occasionally.

Wold became intrigued when a Scottish patient on a message board mentioned in 1998 that his headaches had gone away after he took LSD recreationally. LSD was hard to get in this country, but other patients began reporting that mushrooms, which are similar chemically, helped them, too. Most, he said, consume amounts well below a recreational dose.

Both LSD and psilocybin are considered illegal, schedule I drugs in the United States, meaning they have no accepted medical use and a “high potential for abuse.” State laws vary, but it is generally illegal to possess psilocybin mushrooms. However, Wold said, spores are readily available on the internet, and patients can grow their own. He was not aware of arrests.

Wold’s group has been pushing for high-quality science on mushrooms. Wold, who owns his own construction business and doesn’t have a college degree, was intimidated when he went to Harvard University to beg for research on psychedelics.

The result was a report in the scientific journal Neurology in 2006, based on a survey of 53 cluster-headache patients who had tried mushrooms or LSD on their own. Eighty-five percent of respondents who tried the drugs during attacks said the pain stopped. Fifty-two percent said psilocybin stopped a cluster of headaches. The authors point out that the online survey may have disproportionately attracted people who had gotten good results.

Because the placebo response is notoriously high in pain research, the results should be taken with a grain of salt, but they were a foot in the door.

An intriguing alternative

John Halpern, a Harvard psychiatrist who has studied hallucinogenic drugs and was involved in the Neurology survey, was intrigued enough to pursue further research. Before attempting to get approval to study an illegal substance, he looked at other compounds similar to LSD. He found one, 2-bromo-LSD, that was very much like LSD but did not cause hallucinations. He worked with some German doctors to test that drug, which has few side effects, on patients in Europe.

That very small study – just five patients – was also intriguing. Three doses were able to break a cycle or improve the frequency and intensity of attacks.

Halpern was so convinced that the drug could be useful – and better than psilocybin – that he started a company and began trying to attract pharmaceutical company funding to test it. He got nowhere.

“This can be potentially life-changing,” he said. “It just breaks my heart.”

He recently left Harvard to be medical director of a new addictions-treatment hospital.

Meanwhile, Wold said, a team at Yale University has decided to pick up the work on psilocybin. Yale declined to comment.

Natural substances

Several headache specialists said they couldn’t endorse the use of mushrooms but expressed sympathy with their patients and interest in their results.

“There’s starting to be more of a recognition that some of the naturally occurring substances that haven’t been considered up till now may have a risk/benefit ratio that’s as good or better than things we can prescribe,” Penn’s Detre said.

Several experts said the cluster-headache patients mostly do not seem interested in the recreational effects of the drugs. “I’ve met loads of these people, and they’re not people who have done drugs before,” said Joanna Kempner, a sociologist at Rutgers University who has studied migraine and cluster patients. “They take these drugs very much as medicine.”

Caution on psilocybin

Hannah said he tried mushrooms and the treatment made his headaches worse. He worries that psilocybin might harm patients with psychological problems and wants bigger, scientific studies before urging patients to try it.

Doctors at Jefferson and Penn Medicine said new treatments are in the works. Both systems are testing whether a monoclonal antibody known as LY2951742 (galcanezumab) can prevent both episodic and chronic cluster headaches. It targets the CGRP peptide, which is elevated in migraines and cluster headaches.

Jefferson’s headache center also tested the electroCore vagus nerve stimulator, an electrical device that patients held against the side of their necks during headaches. The vagus nerve runs from the brain stem into the chest and abdomen.

The trial found positive results for episodic, but not chronic, headache. The stimulator is already approved in Europe and Canada.

A current trial is testing the sphenopalatine ganglion (SPG) stimulator, also already in use in Europe, for people with chronic cluster headaches. A study from earlier this year found that 45 percent of the 33 chronic cluster-headache patients in the trial had a positive response to the ATI Neurostimulation System.

Hannah is hopeful that more pharmaceutical companies and device-makers will take an interest in cluster headaches. “There’s money to be made,” he said.

Original Source – Click Here


Great video on Microdosing Psychedelics (Magic Mushroom Psilocybin)

Study: Magic mushrooms are the safest drug

But they’re still illegal.

Disclaimer: Popular Science does not endorse the use of illegal drugs.

If you’re looking to play it safe when it comes to illicit substances, look no further than the humble shroom. It’s non-addictive, hard to overdose on, and you can grow it yourself. And, according to a massive report by the Global Drug Survey, it sends the fewest people to the emergency room of any drug on the market. Take that, meth.

Perhaps the most dangerous thing about psychedelic mushrooms is that they’re easily confused for the poisonous kind. There are over 100 varieties of psilocybin-producing shroomies, which is the chemical that makes you trip when you eat them. Some of them are bound to look like toxic varietals, especially if you’re in a hurry to get high. Just as you should never grocery shop while hungry, you should never go mushroom hunting while jonesing for a trip.

Instead, you should befriend a mycologist (a person who studies mushrooms) so that they can help you find the sort of shroom. Most people who don’t buy their mushrooms tend to pick them themselves rather than grow them, which is the riskier—albeit faster—option. The magic varieties grow on every continent, though if you happen to be somewhere subtropical and humid you’ll find more types. A mycologist friend is extra handy in places like Colombia, New Zealand, Norway, Mexico, Brazil, and Scotland, where the Global Drug Survey shows more than a third of shroom consumers pick their own. In Finland, Germany, the Netherlands, and Belgium, people grow far more than they pick.

It’s actually very easy to grow your own magic mushrooms, and it ensures that you’ll never accidentally poison yourself (as long as you keep an eye out for dangerous mushroom mold). Which is not to say that you should grow them, because possession of hallucinogenic mushrooms or sale of spores with the intent of growing psychedelic mushrooms is strictly illegal in the United States. We’re just saying that if you did grow them, it would be safer than trying to pick them in the wild.

Depending on your proximity to EDM venues versus hippie compounds, LSD might be far easier to come by than magic mushrooms. Five times more people need emergency treatment for LSD than they do for shrooms, though that still puts LSD below alcohol, amphetamines, and synthetic cannabis in terms of safety. Of the 10,000 people who reported taking magic mushrooms, only 17 went to the hospital versus 95 on LSD.

More people probably seek treatment because LSD comes in pill form, where you have no real idea of the dosage (or whether it’s spiked with something else, like rat poison) unless you test it yourself. And honestly, who’s testing it themselves? You’re gonna pop the pill, or maybe pop just half the pill if you’re being a little less foolhardy.

LSD also lasts longer and affects way more receptors in your brain than shrooms do. Psychedelic mushrooms only directly affect your serotonin receptors, whereas LSD affects serotonin, dopamine, and a whole host of other stimulating receptors in your brain. Shrooms may have some indirect effect on dopamine levels, but it’s minimal at best. The longer, potentially more intense results from LSD aren’t likely to do actual damage to your brain. But they are likely to give you a bad trip. And really, that’s the main danger with all psychedelics—if you’re anxious before you start or you begin to feel paranoid, the mind-altering impacts from the drugs only amplify those feelings. People who freak out on bad trips can be a danger to themselves and their friends, and that accounts for most of the related hospital visits. If you really overdid it on the pills, you might need medication to calm you down for a while.

Other than that, hallucinogens are pretty safe. They can reduce anxiety, ease the intense pain of cluster headaches, alleviate OCD symptoms, improve depression, and boost the psychological state of terminal cancer patients. A 2006 double-blind study sponsored by the U.S. government found that about 80 percent of people who took psilocybin reported that their well-being improved and remained that way for months after their psychedelic experience (the control group did not). Even over a year later, participants said that it was one of the most meaningful experience of their lives and that they continued to see benefits of it. Even if some of that is just them expecting to see long-lasting results from a psychedelic experience, it’s certainly compelling.

And you can’t even get addicted to them. Magic mushrooms give you short-term tolerance, which means taking more drugs to try to get a better trip won’t help you. Plus a high (pun intended) dose of mushrooms is more likely to make you paranoid than it is to make you feel the music better. If you can figure out the right dose for your body, you can get almost exactly the same high every time. Maybe that’s why the survey found that psychedelic users were among the most responsible drug users and took the most precautions. After all, reproducibility is the key to good science.

Click here for Story

How Long Until We Can Grow Medicinal Magic Mushrooms: An Investigation

A wave of studies say psychedelics can treat depression, end-of-life anxiety, addiction and more. So we asked experts when Canadians will be able to grow medicinal shrooms at home.

It’s 2017, and legal weed is on the way—close enough that you might even have your first non-criminal session planned out. If you’re corny enough to imagine making history by sparking a joint on the steps of Parliament minutes after the paperwork is signed, it’s worth remembering you won’t be the first legal weed smoker in Canada.

Medical weed, and the right to grow it, has now been on the table for two decades, starting with an epileptic guy named Terrence Parker. After being charged with possession a bunch of times, Parker fought the government and won the right to be exempt from further growing and holding charges in 1997. An appeal court decided that exemption should apply to anyone growing for a medical purpose in 2000. Though regulations tried to outlaw homegrown medicinal bud again in 2013, that was struck down in court last year.

What we haven’t had in Canada (yet) is a legally-sanctioned medical shroom grower. With a wave of recent studies suggesting psychedelics are an effective treatment for depression, end-of-life anxiety, addiction and more, that prospect doesn’t seem as far fetched at it once did. As you can probably imagine, some fans are already looking at Canada’s path to medical weed, and applying the same arguments to magic mushrooms. Will that take another 20 years to grow your own? Or is the legal precedent already set?

Twenty-three-year-old Spencer Allison is on precisely this trip. He’s read much of the new research on psychedelic treatment for depression, as well as a few court decisions, and thinks it’s just a matter of time before he can grow his own medical mushies. Allison’s been bugging a bunch of bureaucrats at Health Canada for a new “section 56” exemption, just like Parker’s in ’97. So far, it’s not going so well.

Allison says he found the Parker case on Wikipedia, and went to the Ontario Court of Appeals site to get a summary of the arguments. “I went through that, hit Ctrl-F, and just started changing every mention of epilepsy to depression, and found anything that applied to marijuana also worked for LSD and other psychedelics.”

Read More: What Are the Medical Benefits of Psychedelics?

Allison thinks the very same argument will eventually force the government to let him legally grow at home. “I think it’s just a matter of when, more or less.” Given all the excitement (and caution) over psilocybin’s medicinal possibilities, I decided to call a few science and legal experts to find out if Allison’s optimism holds up to scrutiny.

When I called up Mark Haden of the Multidisciplinary Association for Psychedelic Studies, aka MAPS, he said weed and mushrooms are entirely different drugs, and their legalization will probably be super different, too. Haden recently put out a paper that laid out how he thinks psychedelics should be regulated in Canada, including a new agency of government-licensed trip sitters.

“The path to legalization of cannabis is completely different. The path to legalization of cannabis has been political,” he told VICE. According to Haden, because psychedelics don’t have the same widespread popularity that weed does, we’ll never see mushrooms on a ballot question in the states, or the right to micro-dose rolled into a major policy plank in Canada’s next election.

But that doesn’t necessarily mean legal shrooms is a long way off, says Haden. Because medicinal tripping is so niche, he says it is more likely to be handled like any other new treatment seeking government approval. “Basically it’s called drug discovery, and any pharmaceutical company who has ever produced a prescription drug is going through the stages we’re going through,” he told VICE.

MAPS is actually in a third stage of clinical trials for MDMA-assisted psychotherapy treatment for victims of trauma, something Haden says is on track to become a prescription by 2021. A second study into the effects of psychedelic mushrooms on depression is at about the same stage, with clinical trials showing promise.

“My understanding is they’re on the same timeline that we’re on,” Haden told VICE. “When we finish our phase three study, we submit our data to Health Canada… and they look at it and say ‘we approve.'”

If all goes well, Haden expects there will be separate certification for growing at home. Patients who get approval from their doctor would perhaps do a weekend training course, to get a basic understanding of setting, safety and dosage. But before we get there—he’s guessing a four to five year timeline—Haden anticipates there’ll be some resistance. For one, psychedelic treatment for depression would hurt the bottom line of any company in the anti-depressants market. But what pharmaceutical companies will do to protect those profits is still “up to speculation,” according to Haden.

Just like with weed, a court challenge could force a decision on the issue. John Conroy was part of the legal team that helped strike down Canadian regulations that banned personal weed growing for medical purposes, and he sees some parallels to the case for psilocybin.

The fact that psychedelic mushrooms grow in the wild makes for a similarly interesting case, according to Conroy. He recalls a decade-old controversy over what to do when mushrooms showed up in farmer’s fields. “I remember going to a meeting many years ago, when it was popular, and hearing people say ‘So what am I supposed to do if the stuff grows wild in my fields? Do I have to smack ’em over the head?'”

But Conway says despite the legal parallels, he hasn’t heard much interest in getting a challenge like that going. “To the best of my knowledge it would be similar to marijuana. You would need a doctor that’s supportive,” Conroy said, adding that there would probably need to be criminal charges brought against the mushroom grower.  “Going into court, you could bring an Allard-type case forward.”

When asked about obstacles, Conway said getting doctors on board to prescribe could be the hardest part. Most of them aren’t into “whole plant” medicine, he said, and medical colleges have pushed back against marijuana policy reform.

But with weed setting the stage this year, both Haden and Conroy seemed to think mushrooms could follow a speedier path to home cultivation. Drawing comparison to other civil rights shifts, Haden sees an extended period of debate and protest leading up to several rapid changes in drug policy.

“When the balloon pops, it pops pretty darn quickly,” he said. ‘Cannabis was the first leaking of air out of the balloon.”

Cannabis related Research and other substances that help me

Psilocybin found in Magic Mushrooms give me the most relief. Here are links to the science behind these amazing substances.

2006 Jun 27

Response of cluster headache to psilocybin and LSD. – PubMed


The authors interviewed 53 cluster headache patients who had used psilocybin or lysergic acid diethylamide (LSD) to treat their condition. Twenty-two of 26 psilocybin users reported that psilocybin aborted attacks; 25 of 48 psilocybin users and 7 of 8 LSD users reported cluster period termination; 18 of 19 psilocybin users and 4 of 5 LSD users reported remission period extension. Research on the effects of psilocybin and LSD on cluster headache may be warranted.

Psilocybin and LSD in the Treatment of Cluster Headache


This treatment, commonly referred to as ‘busting’ is a way of using hallucinogenic tryptamines such as psilocybin to relieve cluster headache.  Many cluster headache sufferers, affectionately called “Clusterheads,” find that small, sub-hallucinogenic doses of these tryptamines can end cluster headache cycles and prevent entire cycles from starting.

It may seem extreme to resort to hallucinogens, but a cluster headache is nothing if not extreme. It’s been called the worst headache, or pain of any kind, known to medicine. It is also called suicide headache, as suicide is known as a thankfully-rare symptom. Many clusterheads facing this beast call it just that: the Beast.

Many medications are effective to some degree. High-volume pure oxygen, or triptans such as Imitrex injections are commonly used to relieve individual attacks. There are many treatments to prevent attacks, including verapamil, lithium and steroids; these vary in effectiveness and severity of side effects.

Tryptamines may be more effective for preventive use, and if used carefully produce fewer side effects by far.   For aborting attacks, they rival oxygen in safety and effectiveness.

Tryptamines have their dangers. Aside from being illegal in most countries, they are powerful drugs and must be respected. Pregnant women and people prone to mental illness should not use tryptamines. While it is not necessary to experience a psychedelic trip in order to treat cluster headache, a trip remains a possibility, and one should be prepared.

These pages are rundown of the protocols and procedures being developed for future research.  These are  not rules for treatment, rather a discussion of ideas and experiences from those using this method and the intention is to foster further research and development. There is much yet to learn and understand – and much to discuss with your physician – before attempting this treatment.

Index of pages:    (all linked below)

warnings,  the psilocybin mushroom,  LSA seeds,  playing well together,  shutting the doorthe dosing methodways to takecoping,  oxygen,  the experience,  keeping track,  how well does this work,  other tryptamines.


  • Do not use tryptamines if you are pregnant, they can cause miscarriage.
  • Do not use tryptamines if you suffer from or are prone to mental illness.
  • Take tryptamines only in the proper mind set and physical setting.
  • Tryptamines have physiological effects.
  • Tryptamines are illegal.
  • We are not doctors. This is not medical advice.
  • Take no medication and use no treatment without consulting a physician.
  • Obtain a through and accurate diagnosis from a knowledgeable doctor or neurologist 
before assuming you suffer from cluster headache.

For more detailed warnings see the WARNINGS page.


Information on this web site is for peer support purposes only. Information included should not replace necessary medical consultations with a qualified health professional to meet your individual health or medical needs, or those of your loved ones.

The information provided on this web site and on the ClusterBusters Message Board is with the understanding that ClusterBusters (or its host websites) is not engaged in rendering professional medical services or advice.

By accessing this web site and the ClusterBusters Message Board, you agree to hold ClusterBusters and its affiliates, its assignees, licensees, owners, officers, moderators, administrators, webmasters and directors harmless from any loss, claim or damage arising from your use of any of the information and ideas contained on the site, including following suggestions or advice posted on the message boards.

We, the Operators of this Website, provide it as a public service to our users.

If you have questions regarding these policies please contact us.


Psilocybin and lysergic acid amide (LSA) are the hallucinogens most used in this method. Both belong to the tryptamine family of chemicals. LSD is another tryptamine effective against clusters, and there may be others, including a relative of LSD that causes no hallucinogenic effects – research is ongoing.

There are natural sources for some tryptamines: psilocybin can be found in the psilocybe family of “magic mushrooms” or “shrooms.” The seeds of certain flowering vines contain LSA. Since most tryptamines are illegal, using natural sources is safer, more reliable and avoids involvement with criminal elements.

For more about psilocybin see THE PSILOCYBIN MUSHROOM

For more on LSA, see LSA – SEEDS OF THE VINE

For more on other useful tryptamines see OTHER TRYPTAMINES


Unfortunately, many of the medications used to treat cluster headache tend to interfere with the effectiveness of the tryptamines. A period of “detoxification,” under a doctor’s supervision of course, is needed to clear these drugs from the system. 

Imitrex and other triptans, steroids such as Prednisone, and many other medications can interfere. Some cluster medications can unpredictably increase the psychedelic effects of tryptamines. There are many medications where little is known, especially those taken for other conditions.

There are effective treatments to use during the “detox” period. Breathing high levels of oxygen through non-rebreather masks is very effective. Large amounts of coffee, or taurine energy drinks drank quickly are favorite emergency treatments. And there are the physical coping techniques: ice packs, hot showers, cold water, hard exercise, intense swearing and any number of strange and extreme things clusterheads do to battle the Beast.


Clusterheads use tryptamine substances in a variety of ways. During a cycle, many take a small to moderate dose of psilocybin or LSA every five days or so, until the cycle stops. In some cases, only two or three doses are needed, others may find they must dose roughly once a week or every two weeks.
Better yet, Clusterheads have found they can take a few small doses before a cluster headache cycle is expected to start, and find the cycle never arrives, or is greatly reduced. Some have had success using even smaller doses to stop individual cluster attacks.

For more informations, see THE DOSING METHOD.


The idea here is to experience the maximum cluster relief with a minimum of psychoactive effects. A moderate dose of psilocybin might cause as much high as a couple of beers, though it is a different kind of high. Small doses can be effective even though the effects are slight to none. With LSA seeds, most people will experience little or no side effects at cluster treatment doses – some report drowsiness, some nothing at all. However, LSA can cause significant psychedelic experiences in some people.

While small doses are enough to treat clusters, tryptamines are powerful hallucinogens and must be used with caution. Those with a tendency toward mental illness should avoid tryptamines or any other hallucinogen. The plan is to minimize the high, but also to prepare for any psychedelic experiences that might come along. Every person is different, and every natural substance – mushroom or seed – may differ significantly in potency. See WARNINGS

There is promising research involving a tryptamine that does not cause significant psychoactive effects, and if it confirmed, could enable many more people to consider this method. To learn more, read HOW WELL DOES THIS WORK?.

For more on the experience of using tryptamines to treat clusters, see THE EXPERIENCE


The effect of tryptamines on clusters can seem like magic at first – surprisingly fast and complete. But it’s not magic, it’s neurochemistry, and it’s not over until the proverbial opera performance ends.

Everyone is different, but there often is an immediate sense of relief, followed within a few hours or a day or two, by the return of cluster attacks. These “slap-backs” can be abnormal attacks – shorter or longer than usual, or more painful or less painful than usual, and coming at odd times. There might be a few or several but these attacks then may begin to fade, at least for a while.

Symptoms may gradually return or continue at a low level, and a repeat dose is needed. For many, two or three doses can end a cycle. Some find they must repeat the dose every week or two, gradually stretching out the time between doses until the cycle ends.

Tryptamines don’t seem to work on some people. For others it is extraordinarily effective. One sufferer of chronic cluster headaches reported being pain-free for years after a single dose. Another reported no relief at all after several relatively strong doses. For more on the results of this treatment see SO HOW WELL DOES THIS WORK?Works Well

The same treatments and coping methods used in the detox period can be used for these “slap-back” attacks and residual symptoms. Oxygen seems to be particularly effective when using the tryptamine treatment. For more on this, see COPING: BUSTER-FRIENDLY TREATMENTS.

Be sure to read the OXYGEN INFORMATION page. Oxygen is a lifesaver for many cluster headache sufferers.


Make no mistake, these substances are illegal, even when only used to treat cluster headaches.

We cannot and do not recommend buying drugs on the street – it’s illegal and dangerous. Drug dealers are hardly the most savory or trustworthy of individuals, and the drugs they sell might not be what they claim.

There are ways to obtain psilocybin and LSA seeds without dealing with a criminal element, but these other ways are also illegal. In fact, it might be more illegal (a felony) to grow your own mushrooms than to buy them from a drug dealer and possess them (often a misdemeanor). This is not how it should be, and the Clusterbusters hope for a day when drug laws are more rational.

Tryptamines are illegal.

Most all of them, most everywhere. Now understand – we are not lawyers, this is not legal advice, and the law can be complex and vary widely from place to place. When in doubt consult a licensed attorney familiar with the laws in your location.

Seeds containing LSA might be legal to buy, sell, grow and possess in some places. But not to eat. Eating RC, HBWR and Morning glory seeds is usually illegal. Even to treat cluster headaches.

Psilocybin mushrooms are illegal almost everywhere. They might be legal in the Netherlands, but that could change at any time. There may be countries where the government doesn’t care much about mushrooms being illegal, but you can’t count on that. In some parts of then US, you can have shrooms growing on your land, as long as you can reasonably show you didn’t know about it. But if you pick and eat them, that means you knew about it. In most US states (except Georgia and California), psilocybin mushroom spores can be possessed, but only for educational or scientific purposes. You can look at them with a microscope, but you’re not allowed to grow them into mushrooms. Eating spores doesn’t help – they contain no psilocybin.

LSD is illegal everywhere for anything, unless you have a research license. Which you don’t.

DMT concoctions like Ayahuasca are illegal everywhere unless you belong to certain religions in certain countries, which you don’t. And no, you can’t join these religions over the Internet.

The best thing to do is to assume all tryptamines are always illegal, and discretion is always wise.

For more about legal matters, click here: LEGAL.


In 2006, Dr. John Halpern and Dr. Andrew Sewell reported to the National Headache Foundation Research Summit on their case review study, later published in the journal Neurology. They reviewed reports from Clusterheads and found over 80 percent reported significant relief using tryptamines.

These results confirmed several hundred anecdotal reports of treating cluster headaches with tryptamines. A review of these reports shows about 67 percent of chronic cluster headache sufferers and about 75 percent of episodic sufferers report significant relief. These reports were mostly collected from Internet discussion groups and internet survey forms; they aren’t scientifically valid, but provide dramatic testimony from clusterheads finding relief. More formal research is in the works, see HOW WELL DOES THIS WORK?


We don’t know how this works. The current theory is one of SHUTTING THE DOORThere is informed speculation on how such small amounts of substances can overcome such large headaches, but there is much to be learned. It’s serious neurology, of course. Some ideas seem to center on the way tryptamines constrict blood vessels; others involve the way the indole-ring molecule of the tryptamines fits into seratonin receptors. Particularly interesting is the way small, infrequent doses can have long-lasting effects and seem to work best if taken at intervals of several days.

Of course, it is not magic even if it seems like it, and serious scientific research into the mechanism of both cluster headache and tryptamine effects on the brain would go a long way toward eliminating much massive pain.


Don’t stop reading now. Read everything here. Please don’t use tryptamines without researching and studying the matter thoroughly and consulting your physician.




Do not use tryptamines if you are pregnant; they can cause miscarriage.

Do not use tryptamines if you suffer from or are prone to mental illness.

Tryptamines may interact with other medications.

Tryptamines have physiological effects.

People diagnosed in the past or present with a psychotic disorder, or people with biological parents or siblings diagnosed with a psychotic disorder should not take tryptamines, including LSD, psilocybin, DMT and LSA. Psychotic disorders include schizophrenia, delusional disorder, affective (mood-related) psychosis and others. Tryptamines may exacerbate symptoms of psychosis or trigger psychosis in people who were psychotic in the past, or with immediate family members who were or are psychotic.

Taking tryptamines during or immediately after a period of emotional upheaval, such as a relationship breakup the death of a loved one, may intensify negative emotions, even to a proportion that feels “out of control.”

Tryptamines should only be taken when one feels confident and secure in his or her ability to handle a psychedelic experience and is confident in the stability of one’s mind set.

Tryptamines should be taken only in a place where one feels secure and with people they can trust.

Tryptamines and some of the chemicals found in natural substances containing tryptamines can cause miscarriage. Do not take tryptamines if you are pregnant or think you might be pregnant.

Use of some tryptamines is known to increase heart rate and blood pressure, so consult with your doctor if you suffer any conditions that would be negatively affected by this.

Reynaud’s syndrome (cold-triggered reduction or loss of circulation in fingers and toes) will be made worse by taking a vasoconstrictor, and tryptamines are vasoconstrictors.

People taking lithium, whether for preventing cluster headaches or for some other reason, should not use tryptamines. Anecdotal reports suggest lithium can greatly increase the psychoactive effects of tryptamines and that it can produce very unpleasant feelings, or even symptoms similar to epileptic seizures.

Tricyclic antidepressants, such as Trofanil (imipramine), Anafranil (clomipramine) and others, and MAOIs taken along with tryptamines, may greatly intensify the psychoactive effects.

People with serious liver problems should avoid psilocybin mushrooms as some might have compounds that could affect the liver.


Most all of them, most everywhere. Now understand – we are not lawyers, this is not legal advice, and the law can be complex and vary widely from place to place. When in doubt consult a licensed attorney familiar with the laws in your location.

Seeds containing LSA might be legal to buy, sell, grow and possess in some places. But not to eat. Eating RC, HBWR and Morning glory seeds is usually illegal. Even to treat cluster headaches.

Psilocybin mushrooms are illegal almost everywhere. They might be legal in the Netherlands, but that could change at any time. There may be countries where the government doesn’t care much about mushrooms being illegal, but you can’t count on that. In some parts of then US, you can have shrooms growing on your land, as long as you can reasonably show you didn’t know about it. But if you pick and eat them, that means you knew about it.

In most US states (except Georgia and California), psilocybin mushroom spores can be possessed, but only for educational or scientific purposes. You can look at them with a microscope, but you’re not allowed to grow them into mushrooms. Eating spores doesn’t help – they contain no psilocybin.

LSD is illegal everywhere for anything, unless you have a research license. Which you don’t. DMT concoctions like Ayahuasca are illegal everywhere unless you belong to certain religions in certain countries, which you don’t. And no, you can’t join these religions over the Internet.

The best thing to do is to assume all tryptamines are always illegal, and discretion is always wise.