Tag: psilocybin

04/5/22

The Psychedelic Pendulum and Psychiatry, Part 1

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In November of 2020, Oregon became the first state to legalize the use of psilocybin in therapeutic settings. Measure 109 created a two-year time period during which regulatory details were to be worked out by the Oregon Psilocybin Advisory Board (OPAB). These details would include issues like what qualifications would be required of therapists overseeing those who chose to use psilocybin. Significantly, psilocybin treatment will not be limited to individuals struggling with mental health issues. Anyone 21 or older who passes a screening will be able to access these psychedelic services for “personal development.”

The first draft of rules recommended by the OPAB were made public in February of 2022. Manufacturers will only be permitted to cultivate one of about 200 different types of mushrooms containing psilocybin, Psilocybin cubensis. Some people were concerned with this recommendation, believing the board was also limiting potential benefits. “It is believed that different species promote different types of experiences.”

Psilocybe cubensis was chosen because it’s one of the most popular mushrooms consumed and one of the most studied. Advisory board members also thought that it would be best to start simple, with one mushroom. Other species might be introduced later.

The OPAB also recommended a ban on growing Psilocybe cubensis in wood chips. This is to prevent a rare condition known as wood lover’s paralysis that produces muscle weakness a few hours after hallucinogenic mushrooms grown in wood chips are consumed. Scientists don’t know why this condition occurs. “But it isn’t believed to happen with Psilocybe cubensis.”

The rules also prohibit the chemical synthesis of psilocybin. Measure 109 also requires the state to only license people to set up grow operations who have been Oregon residents for at least two years. Well, at least until 2025. These recommendations are attempting to allow small farmers to set up grow operations and limit the ability of large pharmaceutical companies to move in and potentially dominate the market.

There are other reasons for banning synthesized psilocybin. The synthesis requires using toxic chemicals that have to be extracted before sale so there’s no residue in the final product. Mason Marks, a member of the OPAB, said synthesizing psilocybin is a huge undertaking. “There was some sentiment that that might be maybe unrealistic or overly burdensome, at least initially to expect people to have that level of expertise or equipment in order to do that.”

Manufacturers will have to use clean, food-grade equipment in an area that can be locked. They won’t be permitted to make psilocybin products that may appeal to minors, like in the shape of cartoon characters. Psilocybin is only permitted to be used orally—not with an inhaler, a suppository or an injection. Students will have the opportunity to observe “non-ordinary states of consciousness.”

Facilitators (not therapists?) will have to take at least 120 hours of instruction, covering everything from the history of psilocybin use to safety concerns. They will have to have sufficient experience to teach classes for individuals interested in trying psilocybin. But what about ethical expectations and boundaries with clients under the influence?

Therapeutic facilitators of individuals doing psychedelic therapy from the time of its origins in the 1950s recommended two therapists, one male and one female. This was to minimize the possibility of sexual exploitation of the clients when they are under the influence of psychedelics. More about this in part 2 of the article.

These draft rules need to be discussed and adopted by the Oregon Health Authority. Other rules are still pending, such as how research with psilocybin should be conducted, and the conditions (i.e., schizophrenia) that would prohibit people from trying psilocybin treatment. There are more complicated issues that need to be decided as well. There’s a desire to permit microdosing psilocybin (taking one-tenth or one-twentieth of a normal dose), over a few days. This practice is thought to boost creativity and focus, as well as alleviate depression.

Oregon’s psilocybin system is scheduled to begin in 2023. The Oregon Health Authority will begin taking applications for licenses to manufacture, transport, deliver, sell and purchase psilocybin products on January 2, 2023.

Psychology Today has a page that introduces the reader to “Psychedelic-Assisted Therapy,” giving information on the most common psychedelic substances, their general effects and properties, as well as potential harms and proposed therapeutic uses. It also has a section on “Understanding Microdosing.” The most common psychedelic substances listed on the page were: psilocybin, LSD, ayahuasca, mescaline and MDMA. All but MDMA listed psychosis as a potential harm. Therapeutic uses being investigated include: PTSD, addiction to alcohol, tobacco and cocaine; anxiety associated with terminal illness; depression and general anxiety.

Dependence or substance misuse is not listed as a potential harm for any of the psychedelics, which do have a low risk for addiction. But the repeated therapeutic use of psychedelics increases the ritualized, long-term use of these drugs, and raises the possibility of misuse or dependence problems developing in users over time.

Information on microdosing said there was some evidence of positive effects performance and creativity, but it was mostly anecdotal. One 2018 study published in the journal Psychopharmacology, “Exploring the effect of microdosing psychedelics on creativity,” found support for its cognitive enhancing properties, but fluid intelligence was unaffected. The researchers concluded that while large doses of psychedelics can introduce several undesirable side effects, microdoses might be an alternative that could eliminate the risks of these side effects, while maintaining the benefits on emotion and thinking.

A 2016 study by Roland Griffiths et al, also published in the journal Psychopharmacology, found that when a high dose of psilocybin was administered to patients with a life-threatening cancer diagnosis under supportive conditions, there were “substantial and enduring” decreases in depressed mood and anxiety. It also resulted in increases in measures of quality of life, life meaning, the acceptance of death, and optimism. The effects were sustained for six months.

There has been a veritable flood of articles and research on the supposed benefits of psychedelics, particularly psilocybin and MDMA, over the last several years besides these two Psychopharmacology studies. In 2019, the FDA designated psilocybin therapy as a breakthrough therapy for Usona Institute, the second pharmaceutical company to gain such an approval in that year. The first company, Compass Pathways, is looking at how psilocybin may help with treatment-resistant depression, that is patients who have not improved after trying two different antidepressants. The significance of the second FDA breakthrough approval is related to how it expands the potential market from the relatively small population of individuals struggling with treatment resistant depression to the estimated 17 million with major depressive disorder, according to a statement by Usona:

This is a significant milestone for the over 17 million people in the US who suffer from MDD. Although there are several existing MDD treatments, Breakthrough Therapy Designation recognizes that psilocybin may offer a clinically significant improvement over these therapies. Psilocybin potentially offers a novel paradigm in which a short-acting compound imparts profound alterations in consciousness and could enable long-term remission of depressive symptoms.

Dr. Samoon Ahmad provided a helpful description of how psilocybin affects the brain in a Psychology Today article, “Understanding the Buzz About Magic Mushrooms.” He said psilocin, not psilocybin, seems to be the substance responsible for the psychoactive effects of “magic mushrooms.” Psilocybin and other psychedelics like LSD and mescaline activate the 5-HT1A and 5-HT2A receptors in the prefrontal cortex, which in turn has downstream effects on serotonin and dopamine. “The increase in dopamine is believed to be part of the reason for some of the psilocybin’s effects on mood, such as euphoria, and the commonly reported phenomenon of depersonalization.”

He said the probability of serious adverse events and abuse of psilocybin was low when compared to other classes of abused drugs. The association of the lifetime use of psychedelics and an increased likelihood of mental illness or suicidality “simply does not exist,” according to Ahmad. By associating “lifetime use of psychedelics” and an “increased likelihood of mental illness or suicidality,” Ahmad’s sidesteps how psychedelics can be destabilizing for some individuals who have a past history of psychotic disorders like schizophrenia. See Part 2 for more information on concerns with psychedelic psychotherapy.

Psilocybin can also produce side effects like hypertension, nausea, vomiting, anxiety, confusion and more. Ahmad also pointed out the importance of “set and setting,” the individual’s mindset and their environment.

A positive experience may inspire life-changing epiphanies and grant individuals a greater perspective on life. A negative experience may result in disturbing thoughts or hallucinations, which may lead to anxiety, disorientation, delirium, and, in extreme circumstances, temporary psychosis. Researchers have found that they can significantly diminish the likelihood of negative experiences by providing patients with more preparation and interpersonal support during the period of drug action.

There is still a risk if the interpersonal support is inadequate or inappropriate—not respecting clear, therapeutic boundaries between the support person and the client. And the preparation may not get the person ready for the actual psychedelic experience. Careful attention to the “set and setting,” the inner and outer environments of the drug event, is crucial for a positive experience.

Ahmad said research has shown that psychedelics hold a great deal of promise, “as long as they are administered in a controlled and clinical environment or under the guidance of individuals who are experienced in the use of psychedelics.” But stigma surrounds the use and research into these drugs. His hope is that there will be a loosening of restrictions and regulations in the U.S. as there is more research published, “and the case for the use of psychedelics becomes stronger.”

Dr. Ahmad and researchers like Roland Griffiths (see this Google scholar link for “Roland Griffths psilocybin”) are representative of those who see the potential for psychedelic therapy, particularly with psilocybin. Rick Doblin and his organization MAPS (Multidisciplinary Association for Psychedelic Studies) are attempting to bring MDMA to market as a treatment for PTSD see this Google scholar link for “Rick Doblin MDMA”). British researchers including Robin Carhart-Harris and David Nutt want to treat depression with psilocybin. Michael Pollan, author of a best-selling book on psychedelics, How to Change Your Mind, thought there has been a sea change in attitudes towards psychedelics. In “The Psychedelic Revolution Is Coming,” he said, “Given the mental health crisis in this country, there’s great curiosity and hope about psychedelics and a recognition that we need new therapeutic tools.”

But what are the risks in turning to psychedelics like psilocybin and MDMA as the next great hope in psychiatric drug treatment? As Andrew Jacobs noted in his NYT article, “The Psychedelic Revolution Is Coming,”

The question for many is how far — and how fast — the pendulum should swing. Even researchers who champion psychedelic-assisted therapy say the drive to commercialize the drugs, combined with a growing movement to liberalize existing prohibitions, could prove risky, especially for those with severe psychiatric disorders, and derail the field’s slow, methodical return to mainstream acceptance.

We’ll look at some of the concerns others see with the growing move towards psychedelics as the newest fad in the pursuit of therapeutic tools in Part 2 of this article. For more information on psychedelics as therapy, see the following articles on this website: “Psychedelics Are Not a Magic Bullet,” “The Long, Strange Trip of Psychedelic Psychiatry,” “Give MDMA a Chance?,” and “Psychedelic Renaissance?”

08/3/21

Psychedelics Are Not a Magic Bullet

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The Society for Cultural Anthropology published a series of articles, “The Psychedelic Revival,” which noted that psychedelics were making a comeback in modern science, public discourse, and cultural significance. Popular books and mainstream media have highlighted seemingly promising research with drugs such as MDMA, psilocybin and ayahuasca. The medicalization of psychedelics has stimulated the expansion of institutional research and private investment as these new treatments move towards the market. The New York Times published, “How MDMA and Psilocybin Became Hot Investments.” There is even a webpage for Psychedelic Investors, where you can “find financial backing for your psychedelic-driven idea.”

The NYT noted how the nation’s top universities are setting up psychedelic research centers. Investors are giving millions of dollars to an ever-increasing group of start-ups with psychedelic-driven ideas. Michael Pollan, the author of the best selling How to Change your Mind, said there has been a sea change in receptiveness about what had been considered fringe science. “Given the mental health crisis in this country, there’s great curiosity and hope about psychedelics and a recognition that we need new therapeutic tools.”

The two leading psychedelic candidates being developed as therapeutic tools are MDMA and psilocybin. The journal Nature Medicine published the results of the ongoing quest of Rick Doblin and his organization MAPS (Multidisciplinary Association for Psychedelic Studies) to bring MDMA to market as an FDA treatment for PTSD. The New England Medical Journal just published the findings of a British group of researchers, most notably Robin Carhart-Harris and David Nutt, and their desire to treat depression with psilocybin. Scientists, psychotherapists and entrepreneurs in the rapidly growing field of psychedelic medicine believe it is only a matter of time before the FDA gives approval for these drugs to be used therapeutically.

The question for many is how far — and how fast — the pendulum should swing. Even researchers who champion psychedelic-assisted therapy say the drive to commercialize the drugs, combined with a growing movement to liberalize existing prohibitions, could prove risky, especially for those with severe psychiatric disorders, and derail the field’s slow, methodical return to mainstream acceptance.

Psychedelic research is now swimming in money. Rick Doblin can remember when research money was scarce. But MAPS has raised $44 million over the past two years. “I spend a lot of my time saying no to investors,” said Doblin. John Hopkins, The University of California Berkley, and Mount Sinai Hospital in New York have or soon will have psychedelic research programs funded by private donors.

There are over a dozen psychedelic start-ups and a handful of companies that have gone public. Compass Pathways is a Nasdaq-listed health care company that has raised $240 million and is conducting 22 clinical trials across 10 countries of psilocybin therapy for treatment-resistant depression. Field Trip Health is a two-year old Canadian company trading on the Canadian stock Exchange that raised $150 million to finance dozens of ketamine clinics in North American cities like Chicago, Los Angeles and Houston. Oregon became the first state to legalize the therapeutic use of psilocybin last year. So far, the Justice Department has taken a hand-off approach to enforcing the fact that psychedelics are still illegal under federal law.

Field Trip got its start opening cannabis clinics across Canada. This summer the company plans to test psilocybin therapy in Amsterdam, where psilocybin mushrooms are legal. They are also developing a new psychedelic with the same therapeutic effects of psilocybin, but it works in half the time—about two or three hours. This would reduce the staffing costs of supervised sessions. More importantly, it would give the company propriety control of the new drug. Other biotech companies are doing the same.

Ronan Levy, Field Trip’s executive chairman said, “We are riding the forefront of what I think is going to be a significant cultural and business wave.” This corporate interest is both thrilling and troubling. Potential missteps could undo the progress of recent years. Veteran psychedelic scientists like Charles Grob of UCLA worry that commercialization and the rush toward the recreational use of psychedelics will trigger a public backlash again, “especially if increased availability of the drugs leads to a wave of troubling psychotic reactions.”

Rigorous protocols and a system to train and credential psychedelic medicine professional is needed, according to Grob. They have to be meticulously attentive to safety conditions. If these conditions are not maintained, there is a risk that some people will become psychologically unstable. “And if the primary motivator is extracting profit, I feel the field is more vulnerable to mishaps.” Rick Doblin shares some of those concerns.  “I realize we could screw things up at the last minute so I’m not planning to celebrate any time soon.”

The Pollan Effect

Since the publication of How to Change Your Mind the expectations of participants in the research trials of what’s going to occur have skyrocketed. In “The Pollan Effect,” a psychedelic trial researcher said it was a big problem, but there’s not much they can do about it. The promising results are published and describe an 80 percent success rate and mystical experiences. Then a participant has a session where they don’t feel anything and are hugely disappointed; and sometimes feel like failures. “You want people coming into this with some openness, and typically once you have all these preconceived ideas, they think they know what they want. That doesn’t always work out well.”

For my part I definitely think this issue is a big problem, and my guess is that it will only be getting worse in the near-term. I actually just drew up a slide for a talk at APA [American Psychological Association] next month with the title in bold, PSYCHEDELICS ARE NOT A MAGIC BULLET. I’ll also be talking about . . . this mythology that with psychedelics they can take this brief trip to a faraway place (like Disneyland) and come back magically transformed/cured, whereas the reality is much more complex.

But these warnings don’t seem to discourage the so-called “psychonauts” (someone who explores altered states of consciousness, particularly through hallucinatory drugs). On the maps.org home page is the statement: “Together, we can cross the finish line and make MDMA a medicine.” It adds that if successful, the treatment could transform the lives of millions of people living with complex trauma. Rick Doblin is quoted as saying, “Psychedelics, when used wisely, have the potential to heal us, help inspire us, and perhaps even save us.” And this appears to be the goal behind what MAPS is presenting as MDMA-assisted therapy for PTSD—MDMA-assisted therapy for everyone.

On May 11, 2021, MAPS won an appeal to do a phase 1 trial of MDMA-assisted therapy with healthy volunteer therapists to measure the “development of self-compassion, professional quality of life, and professional burnout among clinicians.” The FDA had placed a clinical hold on the proposed study in 2019 due to concerns regarding the scientific merit of the study, the risk-to-benefit ratio for healthy participants, and the credentials of the clinical investigators. “Personal experience is widely considered to be an important element in preparation and training to deliver psychedelic-assisted therapies.” If the appeal had not been granted, the Lead Facilitator in each two-person facilitator team would be required to hold an M.D., Ph.D. or equivalent degree and be on-site instead of on-call during treatment sessions.

The hoped-for process would seem to be something like this once there is FDA approval for MDMA-assisted therapy for PTSD. Once allowed by the FDA, MDMA-assisted therapy for PTSD would be linked with FDA approval of MDMA-assisted therapy for healthy volunteer therapists; and then followed by FDA approval of MDMA-assisted therapy for any interested, healthy party. Rick Doblin implied as much when he said:

For three decades, we have sought to educate the FDA in our novel approach rather than simply accept FDA requirements that are unjustified by the evidence. The dedicated work and incisive strategy of our Clinical Development team continues to improve the regulatory landscape for all future patients of psychedelic-assisted medicines.

Since 2010, MAPS has organized a series of Psychedelic Science conferences. In 2013, it was a three-day conference with over 1,900 international attendees. The 2017 conference was a six-day global gathering with three days of conference programming. In 2019, the conference became a Psychedelic Science Summit. The 2023 Psychedelic Science Conference expects an estimated 10,000 attendees, “At the world’s largest psychonaut gathering.”

In 2014, Scientific American republished a brief article on the resurgence of in psychedelics as therapeutic agents, which said: “Psychedelic drugs are poised to be the next major breakthrough in mental health care.”  The hype is accelerating and the enthusiasm is growing for psychedelic-assisted therapies. But let’s wait and see what the open science and total transparency of MAPS shows us with MDMA. Remember psychedelics are not a magic bullet, whether they are used to heal or inspire us. They certainly won’t save us and may not be as efficacious as claimed.

In “Trial of Psilocybin versus Escitalopram for Depression,” researchers sought to compare psilocybin-assisted therapy with escitalopram assisted therapy in a randomized, blinded study. The Mental Elf website reviewed and commented on the study. There were no statistically different differences in the primary outcome measure between the psilocybin and escitalopram groups at six weeks, but no conclusions could be drawn from the data. “In both trial groups, the scores on the depression scales at week 6 were numerically lower than the baseline scores, but the absence of a placebo group in the trial limits conclusions about the effect of either agent alone.”

Writing for The Mental Elf, James Rucker and Sameer Jauhar commented how the lack of a placebo control condition made it difficult to differentiate between the two drug treatments and the psychological therapy that went along with these. They noted the six week follow up may not have been long enough to effectively evaluate the escitalopram condition. “Positive and negative expectancy effects are likely to have affected the results in this trial and are liable to bias results in favour of psilocybin.” Given that participants likely received extensive psychological support, “The results of this trial may reflect more the therapeutic efficacy of attentive psychological therapy than to psilocybin or escitalopram.” (emphasis in the original)

05/7/19

Psychedelic Renaissance?

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Spravato (esketamine), a chemical cousin of ketamine (Special K), was recently approved by the FDA as a fast-acting antidepressant. MDMA is now in a Phase 3 clinical trial for PTSD. Psilocybin has received a breakthrough therapy designation for treatment-resistant depression by the FDA. Clinical research into the therapeutic effects of psychedelics has resumed for a variety of conditions, including depression, substance abuse and individuals living with serious medical conditions like cancer. This has led to calls for increasing the availability of psychedelics by loosening the regulatory restrictions that currently limit the drugs’ use for research.

In his book, How to Change Your Mind, Michael Pollan said beginning in the 1990s, a small group of scientists, psychotherapists and so-called “psychonauts,” have sought to resurrect what they saw as a wrongful termination of research into the therapeutic value of psychedelics. “A new generation of scientists, many of them inspired by their own personal experience of the compounds, are testing their potential to heal mental illnesses such as depression, anxiety, trauma and addiction.” Others are using psychedelics in conjunction with brain-imaging technology to explore the links between brain and mind. “The hoary 1960s platitude that psychedelics offered a key to understanding—and ‘expanding’—consciousness no longer looks quite so preposterous.”

Psychedelics are currently classified as Schedule I controlled substances, meaning they have a high abuse potential; no accepted medical use; and have safety concerns, even under medical supervision. Some advocates are calling the DEA to place them into Schedule III, along with ketamine, anabolic steroids and buprenorphine. Writing for Scientific American, Rick Strassman described his own research with DMT in the 1990s. One of the most difficult impediments he faced was DMT being Schedule I.

After nearly two years of close work with FDA and DEA, an effective system developed allowing our studies to proceed. My subsequent applications to use psilocybin and LSD were much more quickly and easily approved. The New Mexico project’s success established the current American regulatory framework that has allowed for the current burgeoning of human studies with psychedelics.

Psychedelics have unique characteristics that make it difficult to fit them into the criteria used to define schedule placement. “Their safety and efficacy exist only within highly structured specialized treatment settings.” Outside of that structure, psychedelics retain their ability for abuse and are capable of debilitating, psychological damage. “How one understands the psychedelic drug state determines the assessment of risks and benefits, and thus drives recommendations for rescheduling.” William Richards, the clinical director for the John Hopkins University psychedelics research program, publicly advocates for the increased availability of the drugs, referring to their ‘inherent spirituality’ in lectures and talks.

Glorifying psychedelics’ benefits and rendering innocuous their adverse effects therefore may explain the Hopkins group’s recent publication of a paper suggesting rescheduling psychedelics into Schedule IV—the most liberal recommendation yet to appear.

Strassman suggested a new category—IA—that would acknowledge psychedelics’ abuse potential, while allowing for their use. “The security requirements established by the DEA for possession of psychedelics for clinical research—background checks of those handling the drugs, secure storage, regular inventory, etc.—would be the same as for Schedule I substances.” Significantly, only those with specialized training would be permitted to administer psychedelics to humans. With such a regulatory structure in place, He thought the clinical promise of psychedelic drugs could be realized without exposing patients to unnecessary risk. “It would also ensure that we maintain scientific rigor, intellectual honesty and high ethical standards as we continue investigating how these drugs produce their fascinating effects.”

One study published in the Journal of Psychopharmacology did produce some interesting effects with psilocybin. Two randomized controlled trials with late-stage cancer patients suggested that a single, high dose of psilocybin had “clinically significant and long-lasting effects on mood and anxiety.” There were no serious adverse events; no participants abused psilocybin; no cases of prolonged psychosis or hallucination. “No participants required hospitalization.”

Single moderate-dose psilocybin, in conjunction with psychotherapy, produced rapid, robust, and sustained clinical benefits in terms of reduction of anxiety and depression in patients with life-threatening cancer. This pharmacological finding is novel in psychiatry in terms of a single dose of a medication leading to immediate anti-depressant and anxiolytic effects with enduring (e.g. weeks to months) clinical benefits. Even though it is not possible to attribute causality of the experimental drug (in terms of sustained clinical benefit) after the crossover, the post-crossover data analyses of the two dosing sequences suggest that the clinical benefits, in terms of reduction of cancer-related anxiety and depression, of single-dose psilocybin (in conjunction with psychotherapy) may be sustained for longer than 7 weeks post-dosing, and that they may endure for as long as 8 months post-psilocybin dosing. The acute and sustained anti-depressant effects of psilocybin in this trial are consistent with a recently published open-label study of oral psilocybin treatment in patients with treatment-resistant depression (TRD) in which psilocybin (25 mg) was associated with 1 week and 3 months post-psilocybin anti-depressant effects.

Reflecting on the results of the study, Stephen Ross, MD, the director of Substance Abuse Services at the Langone Medical Center, said it possibly provides a new model in psychiatry. “This is potentially earth shattering and a big paradigm shift within psychiatry.” David Nutt, MD, PhD, of the Imperial College London said the studies were the “most rigorous controlled studies to date” using psilocybin. Others urged caution applying and interpreting the results. Jeffrey Lieberman, MD, from Columbia University said:

[W]e cannot tell if the anxiolytic and antidepressant effects of the drugs are direct results of their serotonergic effects or secondary to the mystical altered state of consciousness that they produce. Since other serotonergic agonists (eg, lisuride) do not produce this psychedelic experience it has been suggested that psychedelic drugs must bind to the 5-HT2A receptors in a special way or exhibit functional selectivity or receptor bias.”

A study of the abuse potential for psilocybin confirmed low abuse and no physical dependence potential. The study used all 8 factors required to guide the FDA and DEA recommendations for the Controlled Substance Act (CSA). They suggested placement as a Schedule IV Controlled substance. There was “no clear evidence of physical dependence and withdrawal in preclinical or clinical studies, or among those who chronically used illicit products.” The authors said the lack of therapeutic and mechanistic studies of psilocybin and other psychedelics stems from the lack of federal funding for the research and the barriers imposed by a Schedule I classification, not a lack of interest among researchers.

While some psychedelics like psilocybin may be viable therapeutic options, there simply isn’t enough modern controlled trials. James Rucker, MD, MRCPsych, PhD, of the King’s College London Institute of Psychiatry, said: “Psychedelics deserve to be investigated in modern, controlled trials if we are to know whether they are useful treatments in psychiatry, or not . . .  At the moment there isn’t enough high-quality evidence to make that judgment.”

The biggest barrier to their wider use likely stems from the lack of research. Buy there are additional obstacles in doing the research. Most pharmaceutical companies aren’t interested because of the legal obstacles with Schedule I substances and because it’s not profitable to develop treatments with these drugs. The FDA approval of esketamine as a new molecular entity (NME) is the exception. Another problem is the impossibility of using a placebo control or blinding because of the identifiable effects from psychedelics. Finally, there is the challenge of obtaining sources of psilocybin that meet the standards required for the clinical trials. Rucker said:

I think everyone in this field is interested in one thing — that psychedelics get a fair hearing by Western medicine by undergoing well-funded, well-designed controlled trials . . . Then we will know whether they have any benefit, and we can judge whether this benefit is suitably balanced against any harm they might do. Until then we won’t know, and that is a worse state of affairs than knowing.

Benjamin Bell, from John Hopkins University, wrote “The psychedelic renaissance is here.” He is a proponent of psychedelic medicine, and gave a clearly biased history of how research into psychedelics was “turned off,” after Timothy Leary made the phrase “turn on, tune in, drop out” famous. “Researchers in the field are posed at the precipice of progressing forward with revolutionary studies and may conscientiously move our culture forward with them. But moving the culture will require awareness and action from scientists and citizens.” Researchers believing that psychedelics are important and useful need to recognize how that faith is a double-edged sword “and we must remain truly willing to reconsider beliefs in light of new evidence, or it will be impossible to convince the broader public to do the same.”

Researchers have the opportunity and responsibility to properly communicate their findings and recommendations to the public. He thought this was vital if psychedelics were to be integrated into medical use within the wider culture. Meaningfully, he then said: “It is important to remember psychedelics are not the ultimate panacea for treating mental health concerns.” With time and reams of further research, they may become invaluable components of the medical and mental health toolkit. If the research is carefully and systematically done, I’d cautiously agree.

Let’s not repeat the mistake made with marijuana—failing to reschedule it so research into its risks and benefits is easier to do. The science—not the rhetoric—should be the deciding factor in the medicalization and the legalization of psychedelic substances. Rescheduling psychedelics as suggested by Rick Strassman seems reasonable and would permit the researchers holding back from doing psychedelic research to forge ahead. Some psychedelics, like psilocybin, appear to have potential while ketamine and the ketamine knockoff Spravato increasingly ring alarm bells for me because of their abuse potential and the quickness with which their effects seem to fade. For more information on ketamine and esketamine, see: “Hype and Concern with Esketamine” and “Is Ketamine Really Safe & Non-Toxic?”

09/29/14

Psychoactive Science or Sideshow

© Randomshots | Dreamstime.com - Medicine Wagon Photo
© Randomshots | Dreamstime.com – Medicine Wagon Photo

There is a growing call to permit research into the therapeutic benefits of a variety of psychoactive drugs currently classified by the DEA as Schedule 1 controlled substances. The editors of Scientific American called for the U.S. government to move LSD, ecstasy, marijuana and others into Schedule 2, with cocaine, methamphetamine, fentanyl and Ritalin. They point out that such a move would not lead to decriminalization, “but it would make it much easier for clinical researchers to study their effects.”

Schedule 1 controlled substances are “drugs with no currently accepted medical use and a high potential for abuse.” They are seen as the most dangerous drugs, “with potentially severe psychological or physical dependence.” Schedule 2 controlled substances are “drugs with a high potential for abuse, less abuse potential than Schedule 1 drugs, with use potentially leading to severe psychological or physical dependence.”

British researchers have also called for greater access to “classical hallucinogens” such as psilocybin (magic mushrooms, another Schedule 1 drug) and LSD for research into treating depression.

Classical hallucinogens alter the functioning of this system [serotonergic], but not in the same way current medications do: whilst there are identified receptors and neurotransmitter pathways through which hallucinogens could therein produce therapeutic effects, the neurobiology of this remains speculative at this time.

These drugs are all caught in a catch-22, de facto ban on their use in medical research because of their Schedule 1 placement. “These drugs are banned because they have no accepted medical use, but researchers cannot explore their therapeutic potential because they are banned.” Three United Nations treaties extend similar prohibitions to rest of the globe, further complicating their reclassification as Schedule 2 drugs.

British psychiatrist David Nutt has argued that the U.N. charters are outdated and restrict doctors and scientists from studying hundreds of drugs.  He likened this “research censorship” to the Catholic Church banning Galileo from teaching or defending heliocentric ideas in the 1600s. Nutt suggested the Catholic Church banned the telescope, but the ban was actually on books that taught Copernican beliefs.

Nevertheless, he called the laws, which do not discriminate between research and recreational drug use relics of another age. “These laws serve no safety value. . . . The licenses and bureaucracy surrounding them can increase the costs of research tenfold, further limiting what is done.”  Dr. Nutt commented on how LSD and other hallucinogens like psilocybin had potential to explore and treat the brain. “Other therapeutic targets for psychedelics are cluster headaches, OCD and addiction.”

The argument for reclassifying psychoactive substances like marijuana, LSD, ecstasy and psilocybin from Schedule 1 to Schedule 2 has its pros and cons for me. The above discussion presents the case for reclassification, permitting future research into these substances. IF the ideal of rigorous, methodical research into the therapeutic potential of these drugs is followed, all is well.

But we are now in the midst of an epidemic of prescription drug abuse that came through the very same gauntlet of review and approval that these known recreational drugs would pass through to become medicinal agents once they were reclassified. And while there are potential therapeutic applications for marijuana, the current state of medical marijuana looks more like the older sideshow of patent medicines, where you could get cocaine toothache drops, heroin for cough relief, and Mrs. Winslow’s Soothing Syrup (which contained morphine) for teething discomfort.

UntitledIf special interest groups can be held off from bringing about a new age of snake oil salesmanship, then reclassifying these substances and permitting legitimate scientific research makes sense. Done correctly, it might even demonstrate that some of the existing curative claims for medical marijuana and other substances were false. But if these psychoactive substancess achieve FDA approval for any reason, they could be prescribed “off label” as is currently the case with other FDA approved drugs.