Trending Clinical Topic: Psychedelics

Ryan Syrek


April 22, 2022

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Research into how psychedelics cause alterations in awareness, and studies examining use of the drugs in various psychiatric conditions, resulted in this week's top trending clinical topic. A new study examined changes in specific neurotransmitter systems and brain regions that may be responsible for various experiences associated with a psychedelic "trip" (see Infographic below).

Investigators used machine learning to link psychedelic experiences to 40 different neurotransmitter subtypes likely responsible for inducing them. "Hallucinogenic drugs may very well turn out to be the next big thing to improve clinical care of major mental health conditions," senior author Danilo Bzdok, MD, PhD, associate professor, McGill University, Montreal, Canada, said in a press release. Bzdok added, "Our study provides a first step, a proof of principle, that we may be able to build machine-learning systems in the future that can accurately predict which neurotransmitter receptor combinations need to be stimulated to induce a specific state of conscious experience in a given person."

This research is just part of a growing body of evidence that seeks to separate clinical fact from fiction regarding psychedelics. For example, a recent study explored the commonly held belief that use of the drugs can trigger suicidal thoughts, actions, or other types of self-harm. The meta-analysis found that psychedelic therapy was actually associated with large, acute, and sustained decreases in suicidality across a range of clinical patient populations. The analysis included seven psychedelic therapy clinical trials. Five involved psilocybin plus psychotherapy, and two used ayahuasca plus psychotherapy. All seven trials had a "low" risk for bias. The meta-analytic results showed significant decreases in suicidality at all acute time points (80-240 minutes post administration) and at most post-acute time points (1 day to 4 months post administration).

In terms of specific psychedelics, new researched examined the brain scans of almost 60 patients with resistant depression treated with psilocybin. Two studies were involved. The first was an open-label trial of oral psilocybin. Patients had baseline clinical assessment and resting-state functional MRI, followed by fixed-order "low" (10 mg) and "high" (25 mg) psilocybin therapy dosing days separated by 1 week. Brain network modularity was significantly reduced 1 day after psilocybin therapy in 10 of 16 participants. This result implies an increase in functional connectivity between the brain's main intrinsic networks. Pre- vs post-treatment change in modularity significantly correlated with change in Beck Depression Inventory (BDI) score at 6 months, relative to baseline. The results imply that decreased brain modularity 1 day after psilocybin therapy relates to long-term improvements in symptom severity.

The second study was a double-blind phase 2 randomized controlled trial comparing psilocybin with escitalopram. Patients received either 2 × 25 mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily placebo ("psilocybin arm") or 2 × 1 mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily escitalopram (10-20 mg) ("escitalopram arm"). Functional MRI was recorded at baseline and 3 weeks after the second psilocybin dose. On average, BDI-measured reductions in depressive symptom severity were significantly greater under psilocybin than escitalopram, indicating superior efficacy.

The effects of psilocybin on depression appear to be durable, according to a separate study. Substantial antidepressant effects may last at least 1 year in some patients with major depressive disorder (MDD). The study involved 24 adults who met criteria for a moderate to severe episode of MDD as defined by a score of 17 or greater on the GRID-Hamilton Depression Rating Scale (GRID-HAMD). After 6-8 hours of preparatory meetings, participants received two doses of psilocybin at 20 mg/70 kg and 30 mg/70 kg spaced roughly 2 weeks apart. For most participants, GRID-HAMD scores decreased from 22.8 at baseline to 8.7 at 1 week, 8.9 at 4 weeks, 9.3 at 3 months, 7.0 at 6 months and 7.7 at 12 months after treatment.

Given the promise of psilocybin, MDMA, and other psychedelics in treating various psychiatric disorders, further research is needed into how these drugs interact with traditional psychiatric medications. A review examining these interactions found 40 studies dating back to 1958, including 26 randomized controlled trials, 11 case reports, and three epidemiologic studies. Only one randomized clinical trial evaluated the interaction between psilocybin and the most common psychiatric treatment, selective serotonin reuptake inhibitors. Some experts are concerned that the lack of evidence about drug-drug interactions may lead clinicians to taper patients off of traditional psychiatric medications before initiation of psilocybin therapy.

As clinicians caring for patients with psychiatric conditions consider the use of psychedelics, key questions must be answered. This explains why recent findings on the mechanisms and efficacy of the drugs were met with such interest, leading to this week's top trending clinical topic.

Learn more about hallucinogen use.


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