Expert Commentary

Reporting on psychedelics research or legislation? Proceed with caution

Despite the hype, optimism and legislation involving the therapeutic potential of psychedelics, researchers warn that there's much we don't know. This research roundup looks at some of the knowns and unknowns of psilocybin, MDMA and other hallucinogens.

psilocybin mushrooms growing on grass in a forest.
Photo by Igor Omilaev on Unsplash

More cities and states are introducing bills to decriminalize and regulate access to psychedelic drugs, which could potentially become another option to treat mental health conditions and substance use disorders. But the substances remain illegal under U.S. federal law and scientific evidence about their effectiveness is still far from conclusive.

This month alone, California lawmakers introduced a bill to allow people 21 and older to consume psychedelic mushrooms under medical supervision. In Massachusetts, lawmakers are working on a bill that would legalize psilocybin, the active ingredient of psychedelic mushrooms. And Arizona legislators have also introduced a bill that would make psychedelic mushrooms available as a mental health treatment option.

Last December, Congress passed legislation that included funding for psychedelic clinical trials for active-duty service members. And in January this year, the Department of Veterans Affairs announced that it will begin funding research on MDMA, also known as ecstasy, and psilocybin, to treat veterans with post-traumatic stress disorder and depression. This is the first time since the 1960s that the VA is funding research on such compounds, according to the department.

The rise of proposed and passed legislation in recent years necessitates more journalistic coverage. But it’s important for journalists to go beyond what the bills and lawmakers say and include research studies about psychedelics and note the limitations of those studies.

Major medical organizations, including the American Psychiatric Association, have not yet endorsed psychedelics to treat psychiatric disorders, except in clinical trials, due to inadequate scientific evidence.

The authors of a 2023 study published in the journal Therapeutic Advances in Psychopharmacology, also advise “strong caution” regarding the hype around the potential medical use of psychedelics. “There is not enough robust evidence to draw any firm conclusions about the safety and efficacy of psychedelic therapy,” they write.

Scientists are still trying to better understand how psychedelics work, what’s the best dose for treating different mental health conditions and how to reduce the risk of potential side effects such as intense emotional experiences or increased heart rate and blood pressure, the authors of a February 2024 study published in the journal Progress in Neuro-Psychopharmacology and Biological Psychiatry write.

In a 2022 study published in JAMA Psychiatry, Dr. Joshua Siegel and his colleagues at Washington University in St. Louis write that while legislative reform for psychedelic drugs is moving forward rapidly, several issues have not been addressed, including:

  • A mechanism for verifying the chemical content of drugs that are obtained from outside the medical establishment.
  • Licensure and training criteria for practitioners who wish to provide psychedelic treatment.
  • Clinical and billing infrastructure.
  • Assessing potential interactions with other drugs.
  • How the drugs should be used in populations such as youths, older adults and pregnant people.

“Despite the relative rapidity with which some have embraced psychedelics as legitimate medical treatments, critical questions about the mechanism of action, dose and dose frequency, durability of response to repeated treatments, drug-drug interactions, and the role that psychotherapy plays in therapeutic efficacy remain unanswered,” Siegel and colleagues write.

What are psychedelics?

Psychedelics are among the oldest class of mind-altering substances, used by humans for thousands of years in traditional or religious rituals.

In 2021, 74 million people 12 years and older reported using hallucinogens, according to the National Survey on Drug Use and Health.

The terms “psychedelics” and “hallucinogens” are used interchangeably in public discourse, but scientifically, hallucinogens fall into three groups based on chemical structure and mechanism of action, according to NIH’s National Institute on Drug Abuse:

  • Psychedelic drugs, also called “classic psychedelics” or simply “psychedelics,” mainly affect the way the brain processes serotonin, a chemical that carries messages between nerve cells in the brain and the body. These drugs can bring on vivid visions and affect a person’s sense of self, according to NIDA. Drugs in this category include:
    • Psilocybin is the active ingredient in psychedelic mushrooms, also known as “magic” mushrooms or shrooms. It’s a Schedule 1 drug in the U.S. under the Controlled Substances Act, which means it has a high potential for abuse and has no accepted medical use. However, some states have decriminalized it, according to NIDA. The drug has also been given the Breakthrough Therapy designation from the FDA, a process to speed up the development and review of drugs, for the treatment of major depressive disorder.
    • LSD, or lysergic acid diethylamide, is a synthetic chemical made from a fungus that infects rye. It’s a Schedule 1 drug.
    • DMT, or dimethyltryptamine, found in certain plants native to the Amazon rainforest, has been used in religious practices and rituals. The plants are sometimes used to make a tea called ayahuasca. DMT can also be made in the lab as a white powder. DMT is generally smoked or consumed in brews like ayahuasca. It’s a Schedule 1 drug.
    • Mescaline, a chemical compound found in a small cactus called peyote, has been used by Indigenous people in northern Mexico and the southwestern U.S. in religious rituals. Mescaline can also be produced in the lab. Mescaline and peyote are Schedule 1 drugs.
  • Dissociative drugs affect how the brain processes glutamate, an abundant chemical released by nerve cells in the brain that plays an important role in learning and memory. These drugs can make people feel disconnected from their bodies and surroundings. Drugs in this category include:
    • PCP, or phencyclidine, was developed in the 1950s as an injectable anesthetic but was discontinued because patients became agitated and delusional. Today it is an illegal street drug. It’s a Schedule 2 drug, which means it has a high potential for abuse, but lower compared to Schedule 1 drugs.
    • Ketamine, a drug developed in the 1960s and used as an anesthetic in the Vietnam War, is approved by the FDA as an anesthetic. It has been shown to play a role in pain management and treatment of depression. It is also illegally used for its hallucinogenic effects. It is a Schedule 3 drug, which means it has a moderate to low potential for physical and psychological dependence. A chemically-similar drug called esketamine is approved by the FDA for the treatment of depression that doesn’t respond to standard treatment.
  • Other hallucinogens, which affect different brain functions and can cause psychedelic and potentially dissociative effects, include:
    • MDMA, or ecstasy, is a synthetic drug that’s a stimulant and hallucinogen. It is a Schedule 1 drug. It has been given the Breakthrough Therapy designation from the FDA for the treatment of PTSD.
    • Salvia is an herb in the mint family that has hallucinogenic effects. It is not a federally controlled drug, but it is controlled in some states, according to the DEA.
    • Ibogaine is derived from the root bark of a West African shrub and is a stimulant and hallucinogen. It is a Schedule 1 drug.

Research on psychedelics

There was a wave of studies on psychedelics, particularly LSD, in the 1950s and 1960s, but they came to a halt when the U.S. declared a “War on Drugs” in 1971 and tightened pharmaceutical regulations. There was little research activity until the early 1990s when studies on drugs such as MDMA and DMT began to emerge.

In 2006, researchers at Johns Hopkins University published a seminal double-blind study in which two-thirds of participants — who had never taken psychedelics previously — said their psychedelic sessions were among the most meaningful experiences of their lives.

“These studies, among others, renewed scientific interest in psychedelics and, accordingly, research into their effects has continued to grow since,” Jacob S. Aday and colleagues write in a 2019 study published in Drug Science, Policy and Law.

In their paper, Aday and colleagues argue that 2018 may be remembered as the true turning point in psychedelic research due to “advances within science, increased public interest, and regulatory changes,” such as psilocybin receiving the “breakthrough therapy” status from the FDA.

Today, there are numerous ongoing clinical trials on the therapeutic potential of psychedelics for different conditions, including substance use disorders and mental health conditions such as depression, anxiety and post-traumatic stress disorder.

Given the growing number of studies on psychedelics, the Food and Drug Administration issued a draft guidance in June 2023 for clinical trials with psychedelic drugs, aiming to help researchers design studies that will yield more reliable results for drug development.

The systematic reviews highlighted below show that there’s a lack of robust study designs in many psychedelic clinical trials. Some have small sample sizes. Some include participants who have used psychedelics before, so when they participate in a randomized controlled clinical trial, they know whether they are receiving psychedelic treatment or a placebo. Or, some include participants who may have certain expectations due to positive coverage in the lay media, hence creating bias in the results.

If you’re covering a study about psychedelics…

It’s important for journalists to pay close attention to study design and speak with an expert who is not involved in the study.

In a February 2024 blog post from Harvard Law School’s Petrie-Flom Center, Leiden University professors Eiko I. Fried and Michiel van Elk share several challenges in psychedelic research:

  • “Conclusions are dramatically overstated in many studies. This ranges from conclusions in the results sections, abstracts, and even titles of papers not consistent with the reported results.”
  • “There is emerging evidence that adverse events resulting from psychedelic substances are both common and underreported.”
  • Some studies don’t have control groups, which can create problems for interpreting results, “because treatments like psychedelics need to be compared against a placebo or other treatment to conclude that they work beyond the placebo effect or already existing, readily available treatments.”
  • “Participants in psychedelic studies usually know if they are in the treatment or control group, which artificially increases the apparent efficacies of psychedelics in clinical studies.”
  • Small sample sizes can affect the statistical power and generalizability of the findings. “Small samples also mean that results are not representative. For example, participants with severe or comorbid mental health problems are commonly excluded from psychedelic studies, and therefore results may look better in these studies than in real-world psychiatric settings.”
  • Many studies do not include long-term follow-ups of participants. “Studying how these people are feeling a few days or weeks after they receive treatment is not sufficient to establish that they are indeed cured from depression.”

Fried and van Elk also have a useful checklist for assessing the quality and scientific rigor of psychedelic research in their 2023 study “History Repeating: Guidelines to Address Common Problems in Psychedelic Science,” published in the journal Therapeutic Advances in Psychopharmacology.

Journalists should also remind their audiences that the drugs are still illegal under federal law and can pose a danger to health.

In California, the number of emergency room visits involving the use of hallucinogens increased by 54% between 2016 and 2022, according to a January 2024 study published in Addiction. Meanwhile, the law enforcement seizure of psychedelic mushrooms has risen dramatically, increasing nearly four-fold between 2017 and 2022, according to a February 2024 study published in the journal Drug and Alcohol Dependence.

Below, we have curated and summarized five recent studies, mostly systematic reviews and meta-analyses, which examine various aspects of psychedelic drugs, including legislative reform; long-term effects; efficacy and safety for the treatment of anxiety, depression and PTSD; and participation of older adults in clinical trials. The research summaries are followed by recommended reading.

Research roundup

Psychedelic Drug Legislative Reform and Legalization in the US
Joshua S. Siegel, James E. Daily, Demetrius A. Perry and Ginger E. Nicol. JAMA Psychiatry, December 2022.

The study: Most psychedelics are Schedule I drugs federally, but state legislative reforms are changing the prospects of the drugs’ availability for treatment and their illegal status. For a better understanding of the legislative reform landscape around Schedule I psychedelic drugs, researchers collected all bills and ballot initiatives related to psychedelic drugs that were introduced into state legislatures between 2019 and September 2022. They used publicly available sources, including BillTrack50, Ballotpedia and LexisNexis.

The findings: In total, 25 states considered 74 bills, although the bills varied widely in their framework. A majority proposed decriminalization but only a few would require medical oversight and some would not even require training or licensure, the authors write. Ten of those bills became law in seven states — Colorado, Connecticut, Hawaii, New Jersey, Oregon, Texas and Washington. As of August 1, 2022, 32 bills were dead and 32 remained active.

The majority of the bills — 67 of them — referred to psilocybin; 27 included both psilocybin and MDMA; 43 proposed decriminalization of psychedelic drugs.

To predict the future legalization of psychedelics, the authors also created two models based on existing medical and recreational marijuana reform. Using 2020 as the year of the first psychedelic decriminalization in Oregon, their models predict that 26 states will legalize psychedelics between 2033 and 2037.

In the authors’ words: “Despite the relative rapidity with which some have embraced psychedelics as legitimate medical treatments, critical questions about the mechanism of action, dosing and dose frequency, durability of response to repeated treatments, drug-drug interactions, and the role psychotherapy plays in therapeutic efficacy remain unanswered. This last point is critical, as a significant safety concern associated with drugs like psilocybin, MDMA, or LSD is the suggestibility and vulnerability of the patient while under the influence of the drug. Thus, training and clinical oversight is necessary to ensure safety and also therapeutic efficacy for this divergent class of treatments.”

Who Are You After Psychedelics? A Systematic Review and a Meta-Analysis of the Magnitude of Long-Term Effects of Serotonergic Psychedelics on Cognition/Creativity, Emotional Processing and Personality
Ivana Solaja, et al. Neuroscience & Behavioral Reviews, March 2024.

The study: Many anecdotal reports and observational studies have reported that psychedelics, even at microdoses, which are roughly one-tenth of a typical recreational dose, may enhance certain aspects of cognition and/or creativity, including coming up with new, useful ideas. Cognition is a “range of intellectual functions and processes involved in our ability to perceive, process, comprehend, store and react to information,” the authors explain. There are established relationships between impaired cognitive functioning and mental health disorders.

Due to limitations such as a lack of rigorous study designs, various populations in the studies and lack of documented dosage, it’s difficult to draw any conclusions about changes that last at least one week as a result of consuming psychedelics.

The authors screened 821 studies and based on the criteria they had set, found 10 to be eligible for the review and meta-analysis. The drugs in the studies include psilocybin, ayahuasca and LSD.

The findings: Overall, there was little evidence that these psychedelics have lasting effects on creativity. Also, there was not sufficient evidence to determine if this group of psychedelics enhances cognition and creativity in healthy populations or improves cognitive deficits in the study populations.

Pooled data from three studies showed lasting improvement in emotional processing — perceiving, expressing and managing emotions.

The studies offered little evidence suggesting lasting effects of psychedelics on personality traits.

In the authors’ words: “Results from this study showed very limited evidence for any lasting beneficial effects across these three psychological constructs. However, preliminary meta-analytic evidence suggested that these drugs may have the potential to cause lasting improvement in emotional recognition time. Future studies investigating these constructs should employ larger sample sizes, better control conditions, standardized and validated measures and longer-term follow-ups.”

The Impact of Psychedelics on Patients with Alcohol Use Disorder: A Systematic Review with Meta-Analysis
Dakota Sicignano, et al. Current Medical Research and Opinion, December 2023.

The study: Researchers are exploring the psychedelics’ potential for the treatment of alcohol use disorder, which affected nearly 30 million Americans in 2022. The authors of this study searched PubMed from 1960 to September 2023 for studies on the use of psychedelics to treat alcohol use disorder. Out of 174 English-language studies, they selected six studies that met the criteria for their analysis.

The findings: LSD and psilocybin are promising therapies for alcohol use disorder, the authors report. However, five of the six trials were conducted in the 1960s and 1970s and may not reflect the current treatment views. Also, four of the six studies included patients who had used psychedelics before participating in the study, increasing the risk of bias.

In the authors’ words: “Despite the existence of several clinical trials showing relatively consistent benefits of psychedelic therapy in treating alcohol use disorder, there are important limitations in the dataset that must be appreciated and that preclude a conclusive determination of its value for patient care at this time.”

Older Adults in Psychedelic-Assisted Therapy Trials: A Systematic Review
Lisa Bouchet, et al. Journal of Psychopharmacology, January 2024.

The study: People 65 years and older have been underrepresented in clinical trials involving psychedelics, including the use of psilocybin for the treatment of depression and anxiety. About 15% of adults older than 60 suffer from mental health issues, the authors note. They wanted to quantify the prevalence of older adults enrolled in psychedelic clinical trials and explore safety data in this population. They searched for English-language studies in peer-reviewed journals from January 1950 to September 2023. Of 4,376 studies, the authors selected 36. The studies involved psilocybin, MDMA, LSD, ayahuasca, and DPT (dipropyltryptamine), which is a less-studied synthetic hallucinogen.

The findings: Of the 1,400 patients participating in the selected studies, only 19 were 65 and older. Eighteen received psychedelics for distress related to cancer or other life-threatening illnesses. In a trial of MDMA-assisted therapy for PTSD, only one older adult was included. Adverse reactions to the drugs among older patients, including heart and gastrointestinal issues were resolved within two days and didn’t have a long-lasting impact.

In the authors’ words: “Although existing data in older adults is limited, it does provide preliminary evidence for the safety and tolerability of [psychedelic-assisted therapy] in older patients, and as such, should be more rigorously studied in future clinical trials.”

Efficacy and Safety of Four Psychedelic-Assisted Therapies for Adults with Symptoms of Depression, Anxiety, and Posttraumatic Stress Disorder: A Systematic Review and Meta-Analysis
Anees Bahji, Isis Lunsky, Gilmar Gutierrez and Gustavo Vazquez. Journal of Psychoactive Drugs, November 2023.

The study: LSD, psilocybin, ayahuasca and MDMA have been approved for clinical trials on psychedelic-assisted therapy of mental health conditions in Canada and the U.S. However, major medical associations, including the American Psychiatric Association, have argued that there is insufficient scientific evidence to endorse these drugs for treating mental health disorders. To better understand the current evidence, researchers reviewed 18 blinded, randomized controlled trials, spanning 2008 through 2023. Most studies were conducted in the U.S. or Switzerland.

The findings: The studies overall suggest preliminary evidence that psychedelic drugs are mostly well-tolerated. Psilocybin and MDMA therapies may offer relief from depression and PTSD symptoms for at least a year. Most studies also used therapy and psychological support along with psychedelics.

In the authors’ words: “Despite the promising evidence presented by our study and previous reviews in the field, the evidence base remains limited and underpowered. Long-term efficacy and safety data are lacking,” the authors write. “Future steps should encourage and highlight the need for more robust larger scale randomized controlled trials with longer follow-up periods, and efforts to address regulatory and legal barriers through the collaborations between researchers, healthcare professionals, regulatory bodies, and policymakers.”

Additional reading

Therapeutic Potential of Psychedelics: History, Advancements, and Unexplored Frontiers
Juliana Marino Maia, Bruna Stefane Alves de Oliveira, Luiz G.S. Branco and Renato Nery Soriano. Progress in Neuro-Psychopharmacology and Biological Psychiatry, April 2024.

Aggressive Behaviours Associated with MDMA and Psychedelics: A Narrative Review
Negar Sayrafizadeh, Nicole Ledwos, M. Ishrat Husain and David J. Castle. Acta Neuropsychiatrica, February 2024.

MDMA-Assisted Psychotherapy for PTSD: Growing Evidence for Memory Effects Mediating Treatment Efficacy
Mesud Sarmanlu, Kim P.C. Kuypers, Patrick Vizeli, Timo L. Kvamme. Progress in Neuro-Psychopharmacology and Biological Psychiatry, January 2024

Psychedelic Therapies Reconsidered: Compounds, Clinical Indications, and Cautious Optimism
Jennifer M. Mitchell and Brian T. Anderson. Neuropsychopharmacology, July 2023.

Psychedelics as Therapeutics: Gaps, Challenges and Opportunities
An NIH workshop with video recordings. January 2022.

Trends in MDMA-Related Mortality Across Four Countries
Amanda Roxburgh, et al. Addiction, March 2021.

The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future
Robin L. Carhart-Harris and Guy M. Goodwin. Neuropsychopharmacology, October 2017.

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