Fifty Years After The War on Drugs Began Psychedelic Therapies Are Getting a Second Chance

Psychedelics continue to bear the stigma resulting from the 1960s counterculture and the rigid legal regulations that resulted from it. However, half a century after the government crackdown on psychoactive substances began in the 1970s and 80s, and public perception seems to be softening. We are starting to see psychedelics seep into psychiatry at a time when we need it most.?

Under the weight of a crushing mental health crisis, with minimal pharmacological developments in recent decades, many mental health professionals are considering alternatives. The past decade has produced a large body of groundbreaking research speaking to the efficacy of psychedelics in treating many mental health conditions, including PTSD, Major Depressive Disorder, and end-of-life anxiety.?

Both plant-derived and synthetically produced compounds are being studied in reputable academic centres like Johns Hopkins University, Stanford University, and Imperial College of London, lending credibility to the research and its findings. The vast majority of psychedelic research has focused on Psilocybin, LSD, Ketamine, and MDMA.?

Although we don’t yet understand the exact mechanisms through which these drugs work in the brain, psychedelic experiences seem to loosen stuck ways of feeling and thinking in patients, which often results in remission or diminishment of symptoms related to persistent mental health disorders. For the estimated one-third of individuals who are nonresponsive to traditional antidepressants, alternative options are already available in psychiatric clinics, and it appears there will be more to come.?

Ketamine for Depression

The most widely used psychedelic in psychiatric clinics today is ketamine. The FDA originally approved the drug in the 1970s as a general anesthetic used largely to treat injured soldiers during the Vietnam War. Its medical use soon waned as it became a popular party drug due to its dream-like and dissociative effects. It was classified in the mid-80s as a Schedule III drug by the Drug Enforcement Administration (DEA), meaning it carries a low to moderate potential for dependency.?

In spite of its recreational use as a club drug and subsequent scheduling, research continued over the years and showed that administered in a clinical setting, ketamine could be effective in relieving symptoms associated with treatment-resistant depression. Though its FDA-approved medical indication as an anesthetic remains, some clinicians have administered ketamine infusions for off-label use for decades with successful outcomes.?

However, these treatments are expensive because insurance companies don’t cover the cost of drugs for off-label use. Prohibitive costs kept these potentially life-saving treatments out of reach for many until a recent alternative emerged.

In 2019 the FDA approved esketamine, also known as Spravato, which is a nasal spray used for treatment-resistant depression. For safety reasons, this treatment is only available in certified medical offices. It requires the patient to be monitored by a health care provider for up to two hours after administration.

In spite of its relatively high safety profile, ketamine remains illegal for use outside of clinical settings, and potentially negative effects of long-term use have not yet been studied.

Psilocybin-Assisted Therapy

Many see psilocybin as the next legal psychedelic to become available for mental health treatment in clinical settings. On the heels of substantial research focused on the psychoactive property of so-called magic mushrooms, several cities and states across North America have decriminalised the drug.?

In 2020, Oregon passed Measure 109, which tasked the Oregon Health Authority (OHA) with licensing and regulating psilocybin service providers to administer mushrooms to individuals who are 21 or older.?

The two-year development period allotted to the OHA with the passage of Measure 109 to establish regulations regarding the manufacture, delivery, and administration of psilocybin is coming to its conclusion. As of January 2023, individuals who have completed a state-approved facilitator certification program can apply for state licensure to begin their practice.?

In many ways, all eyes are on Oregon to see how their rollout of legal psilocybin services unfolds. Select reputable universities like the California Institute of Integral Studies have already begun certifying psychiatrists and psychotherapists to conduct psychedelic-assisted therapy in anticipation of the legalisation of such treatment.

MDMA For Treatment of PTSD?

The use of MDMA in conjunction with psychotherapy for treating mental health disorders began in the 1970s. Like its psychedelic counterparts, MDMA, also known as Ecstasy or Molly, shortly after became a popular recreational drug in the 80s, triggering a government clampdown. In 1985 the DEA classified MDMA as a Schedule I substance, making it illegal to possess.?

In spite of its scheduling, MDMA research continued, largely driven by the Multidisciplinary Association for Psychedelic Studies founded by Rick Doblin. In 1996 MAPS completed Phase 1 clinical trials of MDMA-assisted therapy for the treatment of PTSD. The success of the trials eventually led to the FDA granting the drug a Breakthrough Therapy Designation in 2017. More recently, phase 3 clinical trials showed that 67% of participants with severe PTSD in the MDMA group no longer met the diagnostic criteria as opposed to 32% in the placebo-controlled group.?

FDA approval of MDMA-assisted therapy hinges on the results of a second round of phase 3 clinical trials currently underway. If the results remain consistent with the positive outcome of the previous trial, some predict FDA approval could come as soon as 2023. It’s possible that the success of these studies will lead to further research with MDMA to treat additional conditions such as eating disorders, substance use disorders, depression, and end-of-life anxiety.?

According to the US Department of Veteran Affairs, 6% of the population will have PTSD at some point in their lives and approximately 12 million suffer from the condition in any given year in that country. The results of phase 3 clinical trials suggest that MDMA has the potential to provide a window of tolerance for participants to revisit and process memories associated with their trauma without the dissociation and hyperarousal typically experienced. MDMA also appears to enable connection with others, catalysing the efficacy of psychotherapy during an MDMA experience.?

A Second Look at LSD

Lysergic acid diethylamide (LSD) carries the most storied history of all psychedelic drugs. Originally synthesised in 1943, it’s the drug most commonly connected to the social unrest associated with the counterculture of the 1960s. Fraught with controversy, the moral hysteria induced by the recreational use of LSD eventually led to the criminalisation of psychedelic drugs.?

However, before its criminalisation, researchers saw potential in using LSD to treat various mental health conditions. Cutting-edge researcher and psychiatrist Humphry Osmond experimented with LSD in the 1950s to treat alcohol dependency. He reported that out of 2000 alcoholic participants who were administered LSD under carefully controlled conditions, 40-45% were still sober a year after the treatment.?

The political and cultural turmoil of the 60s halted research into the drug's efficacy entirely. But in recent decades, a renewed interest in psychedelics has led to modern research that has brought LSD back into the fold. Brain imaging of patients given LSD has shown increased functional connectivity between different regions of the brain. It also appears to have the effect of ego disillusionment and interruption of habitual thought patterns experienced by individuals suffering from mental health disorders.?

There are many unanswered questions regarding the biological and psychological mechanisms of LSD but administered in controlled, therapeutic settings, it’s showing promise as a beneficial treatment. Current research is largely focused on palliative care, substance dependency, and depression.?

Microdosing as an Alternative

The available psychedelic treatments for mental health disorders pose some challenges, even for those with access. Intravenous ketamine, for instance, is not covered by insurance and the cost to the patient is often prohibitive. Psilocybin-assisted therapy will likely present the same financial constraints.

In addition to financial and regulatory issues, many people are hesitant to undergo psychedelic treatment if they have no prior experience. These barriers make microdosing an appealing alternative. Microdosing psilocybin or LSD delivers a sub-perceptual amount of these substances on a daily basis. That means your ability to go about day-to-day life is not impaired, nor do you have to experience the sometimes overwhelming experience of a flood dose of psychedelics.?

Here at MindBio Therapeutics, we have completed Phase I clinical trials prescribing microdoses of LSD to participants who take the drug at home as they would any other drug. We are looking forward to sharing our findings and continuing on the path to making these promising alternative treatments available to those who suffer from mental health disorders.

By MindBio Therepeutics' Health Correspondent Emily Verdoorn

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