Psychedelics for Mental Health
If you search the web for alternative depression treatments, you may find suggestions for things like St. John’s Wort, exercise, massage therapy, yoga, meditation, acupuncture, and hypnosis. These alternative therapies are named as such because they fall outside the standard Western medical model.
The purpose of this piece is not to compare the above-mentioned alternative treatments, nor to examine the currently accepted western medical treatments. Rather, it is to explore the growing research of psychedelic-assisted treatments that are slowly rising in popularity and acceptability due to the hard work and research of passionate individuals and organizations like the Multidisciplinary Association for Psychedelic Studies (MAPS).
This piece is going to look at the evidence of psychedelics’ therapeutic potential for a variety of psychiatric illnesses. First, let’s take a look at the rollercoaster ride of psychedelic history that began with excitement and enthusiasm, met demonization and fear along the way, and is now returning to a positive outlook.
The Beginnings of Psychedelic-Assisted Therapies in the West
Not long after the invention of LSD, interest in the possible use of psychedelic substances to treat mental health problems began to grow. In the 1950s, psychiatrist Dr. Humphry Osmond performed an experiment to evaluate the efficacy of LSD in treating alcoholism. He reported that half of the LSD group either abstained from alcohol or reduced their use, whereas the control group was unchanged.
A much more recent (2012) meta-analysis of 6 trials conducted between the 1960s and 1970s involving over 500 patients found evidence of LSD’s positive effects on alcohol use disorder. Unfortunately, rash drug scheduling decisions put research on hiatus, or we may have known this decades ago. Another drug that showed therapeutic potential but was criminalized before it could be explored was MDMA.
The Agony and the Ecstasy
After the rediscovery of 3,4-methylenedioxymethamphetamine (MDMA for short, not to be confused with regular n-methylamphetamine AKA meth) by pioneering psychopharmacologist Alexander Shulgin, a small network of psychotherapists recognized its potential for mending relationships and engendering psychological healing. Among the individuals Dr. Shulgin introduced to MDMA was psychotherapist Leo Zeff.
According to this New York Times Magazine article, Dr. Zeff was so impressed with MDMA that he trained 4,000 therapists to incorporate it into their therapy. Anecdotally, it was extremely helpful, with some therapists claiming it could produce profound therapeutic breakthroughs in a single session that would otherwise require years of extensive psychotherapy. It is important to emphasize the key role of psychotherapy in MDMA-assisted psychotherapy, however. MDMA is undoubtedly a powerful therapeutic tool, but accompanying psychotherapy is foundational to the treatment’s efficacy.
The early enthusiasm for psychedelics in treating mental health problems didn’t last for long though. As recreational use grew, as well as the association with the counterculture, laws were quickly put in place to stop people from using these substances. Thus, the West returned to a psychedelic dark age.
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Rediscovering the Light: Psychedelics for PTSD
MDMA is proving to be a bastion of hope for thousands of war veterans suffering from post-traumatic stress disorder (PTSD), who have a 50% higher suicide rate than the general US population.
A recent analysis of six phase two trials of MDMA-assisted therapy for the treatment of PTSD found a remission rate of 66.2%, pointing to this synthetic compound’s deeply therapeutic and life-saving potential. The positive outcomes observed in MDMA trials prompted the Food and Drug Administration (FDA) to grant MDMA Breakthrough Therapy Designation in 2017, which extradites the approval process for MDMA-assisted therapy. The classification of MDMA-assisted therapy as a Breakthrough Therapy is indicative of MDMA’s substantial improvement over other currently available treatments for PTSD.
This potentially paves the way to transition MDMA-assisted therapy from the experimental, alternative, and underground treatment categories closer to standard treatment. Doing so would mark a huge shift in attitudes towards psychedelic drugs and add to the body of evidence that they are not just medically useless recreational substances, but can be incredibly powerful therapeutic adjuncts for a variety of difficult-to-treat mental illnesses.
Psychedelics for Anxiety
There is growing evidence that psychedelics like magic mushrooms and LSD can help people deal with the anxiety often confronted during terminal illnesses. A 2021 systematic review that included substances such as psilocybin (the psychoactive compound of magic mushrooms), LSD, ketamine, and MDMA found that psychedelics had positive effects on end-of-life patients’ well-being, quality of life, and easing of anxiety and depression. Furthermore, there were few adverse effects, none of which were serious.
In 2014, Gasser et al. conducted a double-blind, randomized, active placebo-controlled study to investigate the effects of LSD in patients with anxiety associated with life-threatening diseases. Eight participants received two 200 µg doses of LSD in conjunction with psychotherapy 2-3 weeks apart. The remaining three participants first received an active placebo (20 µg LSD), before crossing over to receive a full dose once the initial blinded treatment was finalized. In this trial, two 200 µg doses of LSD combined with psychotherapy produced significant reductions in anxiety in nine participants. Impressively, reductions in anxiety were sustained for at least 12 months.
A recent randomized, double-blind, placebo-controlled Phase II study found that two 200 µg doses of LSD administered in combination with talking psychotherapy to patients with anxiety associated with and without a life-threatening Illness in a calm hospital or practice room produced strong reductions in anxiety, depression, and general psychiatric symptomatology compared with placebo. Reductions in anxiety were statistically significant 16 weeks after the last LSD treatment, while reductions in depression and general psychiatric symptomatology were also sustained for up to 16 weeks.
Psychedelics for Depression
Like MDMA, psilocybin has also been granted Breakthrough Therapy Designation for major depressive disorder and treatment-resistant depression.
A 2020 meta-analysis of eight studies found that psychedelics provide a safe and potentially rapid alleviation of depressive symptoms.
Following this, in 2021, Imperial College of London researchers conducted the first-ever double-blind, randomized, controlled trial comparing the antidepressant effects of a classical psychedelic with a selective serotonin reuptake inhibitor (SSRI). The researchers found that psilocybin administered in a controlled environment with supportive therapy demonstrated similar and potentially superior antidepressant effects than the widely prescribed SSRI medication, escitalopram (Lexapro, Cipralex). However, the study’s authors stressed the importance of conducting larger and longer clinical trials before drawing any strong conclusions regarding psilocybin’s efficacy as an antidepressant.
Since then, a 12-month follow-up study conducted by Johns Hopkins researchers found that psilocybin-assisted therapy significantly reduced depression in 18 of 24 participants diagnosed with treatment-resistant major depressive disorder. More than 50% of participants were observed to be in remission.
British biotech company Compass Pathways recently published the results of their Phase 2b clinical trial. The study — the largest psilocybin therapy trial conducted to date — investigated the antidepressant effects of COMP360, Compass’ proprietary psilocybin formulation, in a cohort of treatment-resistant patients. By week 3, a single 25 mg dose of COMP360 administered as an adjunct to psychological support produced more than a 50% reduction in depressive symptoms in 37% of participants. 29% of participants in the 25 mg group were in remission by week 3.
Compass Pathways did report a high occurrence of adverse serious events in the trial, however. Albeit somewhat expected considering the patient population and the nature of psilocybin’s effects, further research is needed to determine the extent to which serious adverse events were associated with the psilocybin treatment.
Ketamine for Depression
Ketamine is a special case because, unlike LSD or MDMA, which were mistakenly labeled as drugs of abuse with no medical use, or peyote and ayahuasca, which are categorized similarly but available to a few through religious exemption, ketamine has a long history of medical use as a safe and effective anesthetic and even holds a place on the World Health Organization’s essential medicines list.
Ketamine, though not regarded by all as a traditional psychedelic and certainly different in its non-serotonin-focused pharmacology, has been used to treat depression thanks to doctors’ ability to administer FDA-approved drugs for off-label use.
To date, 24 systematic reviews have consistently reported robust and rapid antidepressant effects of ketamine infusions lasting roughly 1-2 weeks. In 2019, ketamine even received full FDA approval as a treatment for major depressive disorder and treatment-resistant depression when given alongside traditional oral antidepressants.
Ketamine has also demonstrated potential clinical efficacy for anxiety, suicidal ideation, PTSD, OCD, and substance use disorders. Interestingly, psilocybin and MDMA have shown similar transdiagnostic therapeutic potential.
Psychedelic Medicine: A Paradigm Shift in Psychiatry?
It seems there has been a great shift in the tides. From the promising research conducted in the ’50s and ’60s to the war on drugs, and now to today’s psychedelic renaissance, the research is finally getting done and the potential of these substances is being explored. Up against mistakes in drug scheduling, a public full of fear, and without the promise of patentable and profitable drugs, brave, passionate people have poured their energies into making what are now sometimes called Breakthrough Therapies more accessible to those they can help.
We cannot view psychedelic therapies as a panacea for mental health problems. Indeed, they are generally not recommended for people with schizophrenia, bipolar disorder, or those that have personal or family histories of said illnesses. As promising as the research looks so far, there is considerably more to be done. That being said, it will be a relief for many patients, families, and doctors to have more tools in the toolbox to battle an array of mental health problems.
Explore By Substance
5-MeO-DMT
5-MeO-DMT (5-methoxy-N, N-dimethyltryptamine) is a short acting, serotonergic psychedelic, found naturally in the venom of the Sonoran Desert Toad (Bufo Alvarius). 5-MeO-DMT is gaining popularity as an effective tool for spiritual exploration and healing due to its extremely powerful psychoactive effects.
Ayahuasca
What is unique about ayahuasca is that it is a concoction of two plants, the combination of which is essential for the ayahuasca experience. Combining two plants to use as medicine may not seem groundbreaking in and of itself, but the fact that if one is taken without the other, the experience is entirely different, and arguably non-existent, is what makes the discovery of ayahuasca so surprising.
DMT
For millennia indigenous-American tribes have consumed N,N-dimethyltryptamine (DMT) as a key ingredient in sacred botanical brews, such as ayahuasca, and snuffs, such as yopo, as part of religious ceremonies in Central and South America.
Ketamine
Though ketamine gained a reputation for being dangerous and easily misused and abused, it wasn’t until 1999 that the US classified it as a Schedule III controlled substance. While it is often associated with the party scene, ketamine therapy is helping change the lives of many with severe depression, PTSD, OCD and even chronic migraines.
LSD
In 1938, a Swiss chemist by the name of Albert Hofmann, working out of Sandoz Pharmaceuticals, became the first man to synthesize Lysergic Acid Diethylamide (LSD). Active at the microgram level (one-thousandth of a gram), LSD is the most potent psychoactive drug known to humankind.
MDMA
The MDMA molecule bears structural resemblance to stimulants and some psychedelics, invoking feelings of euphoria, empathy, and boundless energy. MDMA also intensifies sensory perception, enhancing one’s appreciation of music and color which makes it one of the most popular drugs among festival-goers and electronic dance music fans alike.
Mescaline
In the 16th century, Spanish chroniclers attempted to eradicate ritual use of peyote cactus among indigenous American cultures, which led to the plant’s eventual prohibition in 1720. In the face of adversity, several indigenous communities righteously persevered, continuing and preserving their sacred practice in clandestine secrecy, and even managing to spread it widely over the last 150 years.
Peyote
Peyote is a green spineless cactus that contains the classic psychedelic compound mescaline. Numerous Mesoamerican cultures, including the Huichol (Wixárika), the Cora (náayeri), the Tepehuanes, the Tonkawa, the Mescalero, and the Tarahumara (Rarámuri) have long regarded the plant as sacred, using it in spiritual and healing ceremonies for millennia.
Psilocybin
While shrooms were initially used for ceremonial purposes and spiritual awakenings, they have gained popularity for recreational use and current research on shrooms effects in a therapeutic setting is promising.
San Pedro
Since prehistory, San Pedro has been instrumental to Peruvian cultural traditions. in northern Peru in particular, it has been a tool to facilitate the shaman’s ‘‘journey’’ for healing purposes. Throughout this period, the visionary cactus has been known by many names, including huachuma or achuma.
