Throughout history, psychedelics have been used in spiritual, religious, and healing practices by Indigenous people.

Psychedelics as medicine are deeply connected to human history and have been used safely for millennia. In recent history, however, psychedelics have been thought of more as party drugs or as a way to amplify fun – a perception which falls short of the big picture that psychedelics may play in spiritual practice and even social healing.

Albert Hofmann became the first person to synthesize LSD in 1938. The discovery that LSD could be synthesized in a lab created a scientific and cultural boom in the 1950s and into the 1960s. During the 1970s and 1980s cultural backlash, misinformation and fear began to take over, and research came to a startling halt as government policies were developed.

Despite the fact that psychedelics have been closely connected to humans throughout known history, during this era psychedelics were ultimately labeled as a Schedule 1 Controlled Substance, which prohibited and labeled them as having no medical value. There was little to no evidence that psychedelics presented a medical risk, but the move to Schedule 1 severely dampened education and research efforts.

Fast forward to today though, after decades of education, advocacy, and protest, the numerous health benefits of psychedelics are going mainstream once again. Numerous studies and anecdotal evidence are showing the incredible benefits psychedelics may have for the treatment of PTSD, anxiety, depression, and addiction, as well as being able to inspire creativity.

What are psychedelics?

Psychedelics, or hallucinogens, are a group of substances that create changes in mood, perception, and cognitive functioning. They can alter all senses and affect what we think, hear, and smell, as well as emotions and even our sense of time. Psychedelics can also create hallucinations, and while some of these effects may sound frightening, people often report quite the opposite. Using psychedelics is often thought to be liberating, exciting, fun, and spiritually eye-opening, but it’s essential to emphasize the importance of "set and setting" (more on this below).

In the category of psychedelics are drugs like ayahuasca, LSD, psilocybin, DMT, 2C-B, mescaline, peyote, and salvia. Psychedelics come in many different forms, such as powders, liquids, solids, etc. They can be found in nature (ayahuasca, mescaline) and also be produced in a lab (LSD, 2C-B). Some even naturally occur in our bodies (DMT).

Psychedelics can also be used in many different ways, such as eaten, chewed, smoked, or inhaled. Most users of psychedelics partake only occasionally, and for the most part, psychedelics are consumed in a very different way compared to substances like alcohol or marijuana usage.

Because research on psychedelics has been heavily blocked in recent decades, there is still much to learn in terms of how psychedelics work and what their impact on human health (both mentally and physically) might be.

However, it’s thought that they work by stimulating a serotonin receptor. This particular serotonin receptor, serotonin 2A, seems to be key for activating hallucinogens, and the degree to which hallucinogens "stick" to this receptor impacts potency. Hallucinogens also disrupt and disorganize cortical activity, which, according to leading research, allows the brain to operate in a freer and less constrained way.

What Makes for a Positive Trip?

When talking to someone who has used psychedelics recreationally, you may notice that experiences can be drastically different compared to someone who has used them in a more guided setting. Even if comparing the same person using the same drug, experiences can vary wildly: one "trip" may be illuminating, enlightening, and educational, while the next may be frightening. A large part of this is the set and setting in which psychedelics are taken.

Set refers to the person’s mood, mental state, or state of mind going into the "trip". It can also refer to previous experiences with psychedelics (whether good or bad), expectations, or feelings of excitement, anxiousness, or fear they may be bringing with them into the experience. All of these can greatly impact what happens and what they may get out of their experience.

Setting refers to the environment in which psychedelics are taken. For example, with loved ones, strangers, or alone. This also refers to the physical environment one is in, such as a natural setting, a concert, a party, around large crowds, or in a quiet, relaxed place.

Being with friends or people you trust in a safe and calm place can greatly reduce the risk of having a bad or negative trip.

Medicinal use of psychedelics

It was once believed that using psychedelics could lead to mental disorders such as anxiety, depression, and even psychosis or schizophrenia. The latest research, however, shows that the opposite may be true. Structural changes in neurons might play an important role in depression and other depressive disorders. Psychedelics may be able to change neuron structure in the brain, increasing synapse number and function, which may produce long-lasting antidepressant effects. Psychedelic use has been reported to improve overall emotional well-being, as well as reducing depressive and anxious symptoms according to leading studies.

Psychedelic users also report stronger feelings of connection and community, which can last after the effects of the drug have worn off.

Recent research has shown that psychedelic-assisted therapy may have a future in treating patients with PTSD, depression, addiction, social anxiety, autism, and end-of-life distress. Psychedelic-assisted therapy combines psychedelic usage WITH psychotherapeutic support for people while they are under the influence of psychedelics. In this manner, it is a far different experience from taking hallucinogens at a party or a festival. Because most psychedelics are still classified as Schedule 1 drugs, therapists and mental health professionals may be (understandably) wary of offering this service to patients.

The legality of psychedelics and how times are changing

While there has been a big paradigm shift when it comes to psychedelic usage, especially for possible mental health treatment, psychedelics are still currently prohibited in most countries.

The recent surge of medical attention, books, podcasts, and studies has led to an increase in public demand for the therapeutic interest in psychedelics.

Recently, a few states have begun to change their laws regarding the usage of some of these drugs to treat mental health. For example, Ketamine has been approved by the FDA for treating mental health. Oregon, Washington, California, Colorado, Michigan, and Massachusetts have partially decriminalized or legalized some psychedelics for mental health treatment as well.

3 Questions on psychedelics with Dr. Andrew Weil

What do you think the evolution of psychedelics and medicine will be?

"I think psychedelics will be made legally available for therapeutic use sooner rather than later. Probably first MDMA for the treatment of PTSD, then psilocybin for the treatment of drug-resistant depression, and then we’ll see from there."

Who should be seeking out psychedelic treatment? Who should avoid it?

"I think the only people who should avoid psychedelic treatment are those who have a history of severe mental illness, especially people who have had any psychotic experience or have a low threshold for psychosis. The risks are mainly psychological, and they can be mainly contained by paying attention to set and setting."

What do you think is the biggest benefit of using psychedelics? Any concerns?

"I think the biggest benefits are that they can show you possibilities that you might otherwise not have believed in, both in terms of how the mind functions and how the body functions. I think the main concerns are not having enough people out there who are trained in how to use them and guide people with them."

Watch Dr. Weil talk about psychedelics here:

The Bottom Line: The tip of the iceberg of psychedelics in medicine

While psychedelics have been used for thousands of years in Indigenous cultures and for many decades in underground communities, mainstream culture and medicine are just beginning to catch up to the many incredible opportunities that these substances may offer. Psychedelics may be useful in treating a variety of mood disorders as well as PTSD and social anxiety. The biggest component in using psychedelics in medicine is paying attention to set and setting and using them with skilled practitioners who can guide and support patients through this journey. While it’s an exciting time in medicine, we still have a journey ahead of us.

References:

• Carhart-Harris, Robin, et al. "How Do Hallucinogens Work on the Brain?" BPS, The British Psychological Society, 14 Sept. 2014, https://www.bps.org.uk/psychologist/how-do-hallucinogens-work-brain.
• Darke S, Lappin J, & Farrell M. The Clinician's Guide to Illicit Drugs. United Kingdom: Silverback Publishing, 2019.
• Dean J, Liu T, Huff S, et al. Biosynthesis and Extracellular Concentrations of N,N-dimethyltryptamine (DMT) in Mammalian Brain. Sci Rep 9, 9333 (2019). https://doi.org/10.1038/s41598-019-45812-w
• Doblin RE, Christiansen M, Jerome L, Burge B. The Past and Future of Psychedelic Science: An Introduction to This Issue. J Psychoactive Drugs. 2019 Apr-Jun;51(2):93-97. doi: 10.1080/02791072.2019.1606472. PMID: 31132970.
• Ly C, Greb AC, Cameron LP, et al. Psychedelics promote structural and functional neural plasticity. Cell Reports, 23(11), 3170–3182. https://doi.org/10.1016/j.celrep.2018.05.022
• McClure-Begley T.D., Roth B.L. The promises and perils of psychedelic pharmacology for psychiatry. Nat Rev Drug Discov 21, 463–473 (2022). https://doi.org/10.1038/s41573-022-00421-7
• Nichols D. Psychedelics. Pharmacological Reviews 2016;68:264–355.