Psychedelics Could Be the Next Big Thing in Mental Health Treatment

Psychedelics are a class of powerful, mind-affecting substances commonly referred to as hallucinogens. They alter cognitive processes like consciousness and perception, besides affecting a person’s thoughts, mood, and emotions. LSD, Mescaline (derived from Peyote cacti), Ayahuasca, MDMA, Ketamine, and Psilocybin (derived from so-called ‘magic’ mushrooms) are some of the most well-known psychedelics. Some of these are naturally occurring while others are artificially synthesized. 

Humans have been using psychedelics since prehistoric times in a variety of social, cultural, and ritual contexts. Early research into the therapeutic properties of these drugs peaked in the two decades between 1950 and 1970. Multiple studies in this period showed promising results in the use of psychedelics to treat a host of mental health issues. However, a 1971 decision by the UN Convention on Psychotropic Substances led to psychedelics being outlawed in almost every country, putting a stop to their further testing even under laboratory conditions. 

Over the past few years, the legalization of medical cannabis in several state and national jurisdictions around the world has led to a resurgence of academic and clinical interest in these elusive substances. Researchers from Johns Hopkins Medicine in the US have recently reported that patients with major depression show benefits of psilocybin-assisted therapy for up to a year. Multiple other studies have found psychedelics effective in treating anxiety, treatment-resistant depression, eating disorders, substance abuse, and post-traumatic stress disorder (PTSD), among other mental health ailments.  

Even though psychedelics are considered safe when taken under controlled circumstances and are not known to cause addiction or dependence, it is highly advisable to consult a registered medical practitioner before using any such substance for mental health treatment.

How psychedelics affect the brain

Perhaps the most succinct description of how psychedelics affect the brain is contained in the 1964 book titled The Psychedelic Experience. In it, the authors describe psychedelics as a “chemical key” that “opens the mind, (and) frees the nervous system of its ordinary patterns and structures”.  

In general, hallucinogens cause users to see, hear, and feel things that may seem real but do not actually exist. Psychedelics produce a wide variety of experiences that include disruptions in a person’s capacity to comprehend reality, think rationally, and communicate effectively with others. Others experience transcendental or spiritual experiences marked by stimulating sensations and deep insights. These experiences are typically referred to as a “good trip”. On the flip side, uncontrolled use of psychedelics can result in “bad trips” that are accompanied by nightmarish anxiety and fears of insanity or death. 

Our understanding of how psychedelics actually work in the brain is still evolving and there are contradictory views about it at present. Some studies suggest that psychedelics cause brain regions that work in coordination . to become uncoupled, while other regions that are not directly connected start communicating with each other. Other studies report that psychedelics make neural processes more fluid by reducing the energy required by the brain to switch from one state of activity to another.  

These differences aside, the point on which researchers agree universally is that psychedelics affect neural circuits that use serotonin – a neurotransmitter, or chemical that conveys nerve signals. Ingesting psychedelic drugs activates a serotonin receptor in the brain called 5-HT2A, which disrupts normal neural activity by making nerve cells and neural networks more excitable. These effects occur most prominently in the prefrontal cortex, a region of the brain that is associated with mood, perception, and cognition. Other regions affected by this phenomenon include those that regulate the body’s reaction to stress and panic. 

Advanced neuroimaging technologies like positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) promise to rapidly expand our understanding of how psychedelics affect our brains.  

Psychedelic therapy 

Psychedelic therapy is the use of natural or synthetic psychedelic compounds in the treatment of mental health problems. The therapy is based on the premise that because psychedelic drugs produce powerful psychological changes, some of those changes may persist over longer terms and offer benefits for people suffering from serious mental health issues. In particular, psychedelic therapy is being looked at as a last-recourse option for conditions that have proved resistant to or incurable with traditional treatment techniques. 

Because psychedelics remain classified as Schedule 1 drugs (offering no known medical benefit), psychedelic therapy is still experimental and can be accessed only through regulator-approved clinical trials. There are three distinct types of psychedelic therapy: 

• Only psychedelics: This involves administering a psychedelic drug without any additional drugs or treatments. 
• Guided therapy: This is a form of treatment where a trained professional guides a person through the psychedelic “high” with advice and suggestions.   
• Psychedelic-assisted therapy: This involves the use of traditional psychotherapy techniques in complement with psychedelic drugs. 

Extensive studies over the past couple of years into various psychedelics have left us with a considerable understanding of their different therapeutic benefits. Here are some of the most common psychedelic drugs and the mental health conditions they show promise in treating:   

• LSD: Negative moods, depression, social anxiety, PTSD, and withdrawal symptoms linked to substance abuse. 
• Psilocybin: Anxiety and dread in people with terminal illnesses and depressive symptoms. 
• MDMA: Severe chronic psychiatric conditions like PTSD, anxiety, depression, and substance abuse. 
• Ayahuasca: Mood disorders, treatment-resistant depression, anxiety, and addiction. 
• Ketamine: PTSD, anxiety, depression, and cravings linked to substance abuse.

There is little evidence to suggest psychedelic therapy or controlled use of this category of drugs causes any long-term side effects. Hallucinogen use in general is associated with some short-term side effects like psychosis (a temporary break from reality), fear, and cardiovascular issues like elevated heartbeat and blood pressure. However, these effects are rare and most studies show few or no negative reactions. 

Microdosing for mental health

Microdosing is the practice of ingesting very small doses of a drug to test its potential benefits without incurring the risk of undesirable side effects. In the case of psychedelics, a microdose would fall between 5%-10% of a standard recreational dose. The exact microdose for a particular person is calculated based on their body weight.  

Psychedelic microdosing appeared on the scene more than a decade ago and has been growing in popularity ever since. A Reddit discussion group on microdosing psychedelic drugs that started in 2013 and had 27,000 members by 2018 currently has 229,000 participants. There is hope now that psychedelics could be in for general medical approval like medical cannabis, especially after the US Federal Drug Administration granted ‘breakthrough therapy’ designation to MDMA-assisted therapy to treat PTSD .   

Research has long established the connection between high psychedelic doses and the development of new cellular connections in the brain – a process called neuroplasticity. There is evidence now to suggest that microdosing produces similar neuroplastic effects. These findings are consistent with claims by users that regular microdosing boosts creativity, improves mood, and enhances cognitive and emotional processes.  

One study on psychedelic microdosing found improved mood in more than 26% of participants, while almost 15% reported they had greater focus. Another 2020 study showed evidence of “enduring positive change” in personality, attitudes, and the effects of depression, mood swings, anxiety, and substance abuse. Meanwhile, LSD and psilocybin have shown encouraging results as potential alternative treatments for ADHD, or attention-deficit hyperactivity disorder, in adults.  

While psychedelic microdosing remains a promising field, its effects remain difficult to study in laboratory conditions because of legal and practical limitations. For now, crowdsourced research sites like microdosingsurvey.com and microdose.me are leading the frontline of exploration into the potential benefits of these powerful substances at very low doses. 

Clinical trials  

Research into the therapeutic effects of psychedelics on humans went through an abrupt halt following their 1971 prohibition, before being revived in the mid-’90s by researchers in the US, Germany, and Switzerland. Research over the next two decades has now left us with a considerable body of knowledge on psychedelics. Separate studies have so far established the efficiency of psychedelics in treating particular psychiatric symptoms: Psilocybin has been shown to be effective in the treatment of obsessive-compulsive disorder (OCD), LSD in helping patients with end-of-life psychological distress, and Ayahuasca for the treatment of major depression. 

A host of related studies are currently underway at multiple clinical establishments across the world. These include Johns Hopkins Medicine in the US, where researchers are probing the potential use of psilocybin to help with smoking cessation, Alzheimer’s disease, eating disorders like Anorexia Nervosa, Lyme Disease, and PTSD, among others. Elsewhere in the US, the Multidisciplinary Association of Psychedelic Studies (MAPS) has reported that 67% with moderate to severe PTSD showed remarkable signs of improvement with MDMA therapy in stage III clinical trials. In another study by the mental health care company COMPASS Pathways, 30% of participants with treatment-resistant depression were in remission after a single 25mg dose of psilocybin.  

Results for many more psychedelic trials in mental health treatment are expected to be released in 2023.

When Psychedelics Meet Mental Health

Recently, the use of psychedelics for medicinal purposes in treating mental health illnesses has been gaining traction and receiving dedicated research, showing positive outcomes. This group of drugs, including DMT, LSD, MDMA, and psilocybin, is being explored as a potential game-changer in the treatment of anxiety, depression, PTSD, and addiction.

Listeners are encouraged to reassess their pre-existing biases and assumptions regarding these restricted therapeutics and consider the potential paradigm shift they could bring in the way mindfulness therapy and mental health are approached. Burton J. Tabaac, MD FAHA, presents this thought-provoking perspective.