Psychedelic substances are under investigation in several drug development programs. Controlled clinical trials are providing evidence for safe and effective use of psychedelic therapies for treating mental health conditions. With the anticipated FDA approval of MDMA-assisted therapy for posttraumatic stress disorder in 2023 and psilocybin therapy for depression disorders soon after, now is the time for the medical community to become informed on best practices and to actively participate in developing standards of care for these new treatments. Given the emergence of numerous drug sponsors and other companies developing therapeutic modalities for combination with psychedelic medications, it is essential that the medical professional field is at the forefront of communicating unbiased information related to safety and effectiveness. Gold standards have long been a part of medicine and serve to distinguish treatments and assessments as the highest quality by which all others can be compared to. For a treatment to be established as a gold standard, several factors are considered including the quantity and quality of the supporting data, the rigor of trials, and the safety and efficacy compared to other treatments. In this article, we review the origins of psychedelic-assisted therapy (PAT), minimum requirements for safe use of psychedelics, criteria for gold standards in mental health, and the nuances regarding how to establish gold standards in psychedelic medicine and guide clinical decision making.
safety
Drug Policy Alliance – Real Drug Education
At the Drug Policy Alliance, we believe accurate, honest, compassionate drug education is a right for all young people.
Just Say No’ — Or ‘Just Know’?
My son Johnny, a high school junior this fall, is learning all kinds of new things — academic, social and physical. At 16, he seems fearless. And, as a typical American teenager, he faces two risk-sensitive issues: drug use and sexuality. So I read with keen interest a recent report by the Centers for Disease Control and Prevention that addresses both of these hot-button topics.
Its gist: Teen drug use is up, but fewer young people are having sex, and more of those who do practice ”safe sex.” A decade ago, a third of students surveyed said they had experimented with marijuana. By 1999, almost half had tried pot. But during the same time span, the number of students having sex declined from just over half to slightly under half. Most important: Of those who were sexually active, 58% reported using a condom in 1999, compared with 46% in 1991.
I wanted to know why risky teen sexual activity decreased while drug use rose. A look at our sex and drug education offers an answer: In a nutshell, while we’d all prefer that they abstain from both, we try to reason with teens about sex, but we scare them about drugs.
Principles of Harm Reduction
Harm reduction is a set of practical strategies and ideas aimed at reducing negative consequences associated with drug use. Harm Reduction is also a movement for social justice built on a belief in, and respect for, the rights of people who use drugs.
Human Hallucinogen Research: Guidelines for Safety
There has recently been a renewal of human research with classical hallucinogens (psychedelics). This paper first briefly discusses the unique history of human hallucinogen research, and then reviews the risks of hallucinogen administration and safeguards for minimizing these risks. Although hallucinogens are relatively safe physiologically and are not considered drugs of dependence, their administration involves unique psychological risks. The most likely risk is overwhelming distress during drug action (‘bad trip’), which could lead to potentially dangerous behaviour such as leaving the study site. Less common are prolonged psychoses triggered by hallucinogens. Safeguards against these risks include the exclusion of volunteers with personal or family history of psychotic disorders or other severe psychiatric disorders, establishing trust and rapport between session monitors and volunteer before the session, careful volunteer preparation, a safe physical session environment and interpersonal support from at least two study monitors during the session. Investigators should probe for the relatively rare hallucinogen persisting perception disorder in follow-up contact. Persisting adverse reactions are rare when research is conducted along these guidelines. Incautious research may jeopardize participant safety and future research. However, carefully conducted research may inform the treatment of psychiatric disorders, and may lead to advances in basic science.
Evaluating the Abuse Potential of Psychedelic Drugs As Part of the Safety Pharmacology Assessment for Medical Use in Humans
Psychedelics comprise drugs come from various pharmacological classes including 5-HT2A agonists, indirect 5-HT agonists, e.g., MDMA, NMDA antagonists and κ-opioid receptor agonists. There is resurgence in developing psychedelics to treat psychiatric disorders with high unmet clinical need. Many, but not all, psychedelics are schedule 1 controlled drugs (CDs), i.e., no approved medical use. For existing psychedelics in development, regulatory approval will require a move from schedule 1 to a CD schedule for drugs with medical use, i.e., schedules 2–5. Although abuse of the psychedelics is well documented, a systematic preclinical and clinical evaluation of the risks they pose in a medical-use setting does not exist. We describe the non-clinical tests required for a regulatory evaluation of abuse/dependence risks, i.e., drug-discrimination, intravenous self-administration and physical dependence liability. A synopsis of the existing data for the various types of psychedelics is provided and we describe our findings with psychedelic drugs in these models. FDA recently issued its guidance on abuse/dependence evaluation of drug-candidates (CDER/FDA, 2017). We critically review the guidance, discuss the impact this document will have on non-clinical abuse/dependence testing, and offer advice on how non-clinical abuse/dependence experiments can be designed to meet not only the expectations of FDA, but also other regulatory agencies. Finally, we offer views on how these non-clinical tests can be refined to provide more meaningful information to aid the assessment of the risks posed by CNS drug-candidates for abuse and physical dependence.
This article is part of the Special Issue entitled ‘Psychedelics: New Doors, Altered Perceptions’.
What Do We Know About the Risks of Psychedelics?
For starters, assessing risk is tricky. A lot of what both scientists and the general public think they know about the potential risks of psychedelic use comes from the first wave of research and experimentation in the 1950s, 60s and 70s. But this body of knowledge includes studies that wouldn’t meet today’s scientific standards; urban legends; and sensational, unsubstantiated news stories.
Also, reporting and describing adverse events is often subjective to some extent, psychiatrist Rick Strassman noted in a 1984 paper. Some people consider the drug-induced state itself pathological, he wrote, while others believe even the worst reactions are part of “throwing off ‘straight’ society’s ‘shackles’ and in reaching a ‘higher’ level of consciousness.” And many of the more recent studies on the potential harms of LSD and other hallucinogens draw on data from the 1950s and 60s. Those studies had a lot of methodological problems; many lack baseline data about their subjects, didn’t use placebos and/or failed to specify the source of the drug or the setting in which it was given.
20 Safety Tips for Those Participating in Ceremonies That Use Psychoactive Substances
The WVC acknowledges that a growing number of people throughout the world are participating in ceremonies that use psychoactive substances. We recognize that these rituals can offer participants opportunities for deep healing and self-knowledge. Our community is also troubled by the fact that women who participate in these ceremonies have sometimes been the targets of sexual harassment and assault by shamans and other facilitators. Sadly, the abuse of women by people who present themselves as spiritual leaders is a very old problem that long predates the growing interest in the ceremonial use of these materials. People of all genders have been subjected to these violations.
There is no firm data about the frequency of this misuse of power and many victims are reluctant to publicly discuss their experiences. The WVC is also keenly aware that stories about these types of violations are sometimes sensationalized by the media and those who seek to profit from these accounts. We also make a firm distinction between the regulation of psychoactive substances and practices that could support the safety of those participating in these ceremonies. Some psychoactive substances are legal in certain countries and considered an expression of indigenous medicinal knowledge and religious freedom. Court rulings in the United States and elsewhere acknowledge that the use of these substances is protected from prosecution on religious grounds.
Traditional means of regulation for the ceremonial use of some substances have been in place for many years. Since existing laws against sexual assault are already present in countries where these ceremonies take place, we do not endorse additional government regulations, standards, or controls imposed by perhaps well-meaning groups. History has shown that these measures are often turned against users and producers of such materials and often do not reflect the values of indigenous cultures which have a deep understanding of these substances.
While we do not support additional regulatory frameworks, sexual assault is a crime regardless of the context. Everyone has a right to be treated with respect while participating in these ceremonies. We support accountability for those who lead these ceremonies and measures taken by participants to proactively help secure their own safety. While many shamans and other healers act with great integrity, there are steps you can take to help protect yourself from those that do not. Below is a list of recommendations that may help you effectively prepare for these experiences and reduce the potential for unsafe encounters.
A review of emerging therapeutic potential of psychedelic drugs in the treatment of psychiatric illnesses
Though there was initial interest in the use of psychedelic drugs for psychiatric treatment, bad outcomes and subsequent passage of the Substance Act of 1970, which placed psychedelic drugs in the Schedule I category, significantly limited potential progress. More recently, however, there has been renewal in interest and promise of psychedelic research. The purpose of this review is to highlight contemporary human studies on the use of select psychedelic drugs, such as psilocybin, LSD, MDMA and ayahuasca, in the treatment of various psychiatric illnesses, including but not limited to treatment-resistant depression, post-traumatic stress disorder, end-of-life anxiety, and substance use disorders. The safety and efficacy as reported from human and animal studies will also be discussed. Accumulated research to date has suggested the potential for psychedelics to emerge as breakthrough therapies for psychiatric conditions refractory to conventional treatments. However, given the unique history and high potential for misuse with popular distribution, special care and considerations must be undertaken to safeguard their use as viable medical treatments rather than drugs of abuse.
Psychedelics
Psychedelics (serotonergic hallucinogens) are powerful psychoactive substances that alter perception and mood and affect numerous cognitive processes. They are generally considered physiologically safe and do not lead to dependence or addiction. Their origin predates written history, and they were employed by early cultures in many sociocultural and ritual contexts. After the virtually contemporaneous discovery of (5R,8R)-(+)-lysergic acid-N,N-diethylamide (LSD)-25 and the identification of serotonin in the brain, early research focused intensively on the possibility that LSD and other psychedelics had a serotonergic basis for their action. Today there is a consensus that psychedelics are agonists or partial agonists at brain serotonin 5-hydroxytryptamine 2A receptors, with particular importance on those expressed on apical dendrites of neocortical pyramidal cells in layer V. Several useful rodent models have been developed over the years to help unravel the neurochemical correlates of serotonin 5-hydroxytryptamine 2A receptor activation in the brain, and a variety of imaging techniques have been employed to identify key brain areas that are directly affected by psychedelics. Recent and exciting developments in the field have occurred in clinical research, where several double-blind placebo-controlled phase 2 studies of psilocybin-assisted psychotherapy in patients with cancer-related psychosocial distress have demonstrated unprecedented positive relief of anxiety and depression. Two small pilot studies of psilocybin-assisted psychotherapy also have shown positive benefit in treating both alcohol and nicotine addiction. Recently, blood oxygen level–dependent functional magnetic resonance imaging and magnetoencephalography have been employed for in vivo brain imaging in humans after administration of a psychedelic, and results indicate that intravenously administered psilocybin and LSD produce decreases in oscillatory power in areas of the brain’s default mode network