Psychedelic drugs, including but not limited to psilocybin, lysergic acid diethylamide (LSD), methylenedioxy-methylamphetamine (MDMA), peyote and dimethyltryptamine (DMT), are currently classified by the U.S. Drug Enforcement Administration (DEA) as Schedule 1 controlled substances. This implies that there is no current medical use and there exists a high potential for abuse (DEA, 2021). However, LSD has been of interest to molecular psychiatry for the past 70 years, as its chemical structure is similar to serotonin (5-HT; Tupper et al., 2015). Recently, there has been increased attention on the potential for psychedelic drug treatment of various neuropsychiatric syndromes. Specifically, a growing body of literature suggests utility in the context of trauma- and stressor-related disorders, such as posttraumatic stress disorder (PTSD; Mithoefer et al., 2016).
Psilocybin is one of the heavily studied psychedelic drugs, known as a serotonin partial agonist. It seems to have a significant impact on the 5-HT2A receptor subtype within the cerebral cortex, which may inhibit thalamic filtering through GABAergic projections. In turn, cortical regions are permitted to receive more sensory information (López-Giménez & González-Maeso, 2017). More specifically, the claustrum appears to be a primary target of psilocybin, with effects favoring this region over the bilateral insula and putamen. The drug reduces the functional connectivity of auditory and default mode networks and increases connectivity with the fronto-parietal task control network (Barrett et al., 2020). This is an important consideration in the context of trauma, as the claustrum plays a primary role in the pathways that mediate nociceptive thresholds (Persinger et al., 1997). It is also a component of the larger emotional regulation system that is implicated in trauma-related disorders (White et al., 2015). Effects of 5-HT2A agonism via psychedelics extend to improved tonal musical experiences, mediating connectedness in therapy (Barrett et al., 2018), as well as reductions in alcohol consumption as a result of various stressors (Oppong-Damoah et al., 2019).
The evidence dives deeper into various samples of people experiencing a range of traumas. Psilocybin, MDMA and LSD were all found to result in significant and moderate reductions in traumatic stress symptoms (d = -.45) among individuals who experienced racial trauma (Williams et al., 2020). These results were evident in the 30 days following psychedelic drug use, though this survey-based study did not include a control group. One study investigated the effects of ibogaine, a psychoactive indole alkaloid, among Special Operations Forces personnel. Significant reductions in suicidal ideation, depression, anxiety, PTSD symptoms and cognitive impairment were noted. Overall, 84% of the sample reported the psychedelic experiences as one of the top five personally meaningful experiences of their lives (Davis et al., 2020). An increase in psychological flexibility is noted in several studies as mediating the relationship between these psychedelic experiences and reductions in depression (d = -3.7) and anxiety (d = -3.1), including international samples (Davis et al., 2020; Davis et al., 2019). These reductions were apparent within 30 days following psychedelic treatment. Similar to other survey-based studies on self-reported symptoms and psychedelic drug use, the Davis et al. (2020) study did not include a control group.
Cognitive function is another component that must be considered in the context of psychedelic drug use and trauma. The observed serotonergic system alterations, which are pivotal in the treatment of mood disorders, bring into question how these drugs could impact cognition when, in many cases, cognition is already impacted by traumatic experiences. After a high dose of psilocybin, however, cognitive functions are generally elevated and not negatively impacted (Barrett et al., 2020). For example, negative amygdalar and negative affect responses to facial affect stimuli returned to baseline by the one-month follow-up without reducing positive affect. These results suggest that psilocybin could increase brain plasticity and sustain unimpacted cognitive functions. Studies on psychedelic drug treatment have frequently been limited by their follow-up procedures. Over time, evidence is beginning to suggest that effects are retained up to six months later, with dose-dependent effects (Griffiths et al., 2016; Griffiths et al., 2011).
More recently, MDMA and other psychedelic drugs are being viewed as not only effective on their own, but in the context of psychotherapy. The acute psychedelic effects and the openness described of positive experiences assists with psychotherapy for those who have experienced trauma (Wagner et al., 2017). A clinical trial on MDMA-assisted psychotherapy for those with PTSD has completed Phase 3 (U.S. National Library of Medicine, 2021), which may very well push this treatment into the limelight in regard to its legal status as a non-medical drug. A component in need of focus is one of cultural diversity and inclusion in psychedelic research, as many studies consist of primarily White participants. However, with each scientific advancement comes a new area of study. With the overall goal being to explore this stigmatized area, psychedelic drugs harbor tremendous potential across a variety of symptoms and conditions without evidence of serious adverse effects (dos Santos et al., 2018).
About the Author
Jack C. Lennon is a doctoral candidate in clinical psychology and neuropsychology at Adler University and predoctoral intern at Portland VA Medical Center. He is interested in the impact of various traumas on neuropsychiatric sequelae of neurologic disease.
References
Barrett, F. S., Doss, M. K., Sepeda, N. D., Pekar, J. J., Griffiths, R. R. (2020). Emotions and brain function are alterd up to one month after a single dose of psilocybin. Scientific Reports, 10, 2214. https://doi.org/10.1038/s41598-020-59282-y
Barrett, F. S., Krimmel, S. R., Griffiths, R. R., Seminowicz, D. A., Mathur, B. N. (2020). Psilocybin acutely alters the functional connectivity of the claustrum with brain networks that support perception, memory, and attention. NeuroImage, 218, 116980. https://doi.org/10.1016/j.neuroimage.2020.116980
Barrett, F. S., Preller, K. H., Herdener, M., Janata, P., Vollenweider, F. X. (2018). Serotonin 2A receptor signaling underlies LSD-induced alteration of the neural response to dynamic changes in music. Cerebral Cortex, 28(11), 3939-3950. https://doi.org/10.1093/cercor/bhx257
Davis, A. K., Averill, L. A., Sepeda, N. D., Barsuglia, J. P., Amoroso, T. (2020). Psychedelic treatment for trauma-related psychological and cognitive impairment among US Special Operations Forces veterans. Chronic Stress, 4. https://doi.org/10.1177/2470547020939564
Davis, A. K., Barrett, F. S., Griffiths, R. R. (2019). Psychological flexibility mediates the relations between acute psychedelic effects and subjective decreases in depression and anxiety. Journal of Contextual Behavioral Science, 15, 39-45. https://doi.org/10.1016/j.jcbs.2019.11.004
dos Santos, R. G., Bouso, J. C., Alcázar-Córcoles, M. A., Hallak, J. E. C. (2018). Efficacy, tolerability, and safety of serotonergic psychedelics for the management of mood, anxiety, and substance-use disorders: A systematic review of systematic reviews. Expert Review of Clinical Pharmacology 11(9), 889-902. https://doi.org/10.1080/17512433.2018.1511424
Drug Enforcement Administration (2021). Drug Scheduling. Retrieved from https://www.dea.gov/drug-information/drug-scheduling (accessed May 7, 2021).
Griffiths, R. R., Johnson, M. W., Carducci, M. A., Umbricht, A., Richards, W. A., Richards, B. D., Cosimano, M. P., Klinedinst, M. A. (2016). Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. Journal of Psychopharmacology, 30(12), 1181-1197. https://doi.org/10.1177/0269881116675513
Griffiths, R. R., Johnson, M. W., Richards, W. A., Richards, B. D., McCann, U., Jesse, R. (2011). Psilocybin occasioned mystical-type experiences: Immediate and persisting dose-related effects. Psychopharmacology, 218, 649-665. https://doi.org/10.1007/s00213-011-2358-5
López-Giménez, J. F., & González-Maeso, J. (2017). Hallucinogens and serotonin 5-HT2A receptor-mediated signaling pathways. In A. L. Halberstadt, F. X. Vollenweider, & D. E. Nichols (Eds.), Behavioral neurobiology of psychedelic drugs. Current topics in behavioral neurosciences. Springer.
Mithoefer, M. C., Grob, C. S., Brewerton, T. D. (2016). Novel psychopharmacological therapies for psychiatric disorders: Psilocybin and MDMA. Lancet Psychiatry, 3(5), 481-488. https://doi.org/10.1016/S2215-0366(15)00576-3
Oppong-Damoah, A., Curry, K. E., Blough, B. E., Rice, K. C., Murnane, K. S. (2019). Effects of the synthetic psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI) on ethanol consumption and place conditioning in male mice. Psychopharmacology, 236, 3567-3578. https://doi.org/10.1007/s00213-019-05328-7
Persinger, M. A., Peredery, O., Bureau, J., Cook, L. L. (1997). Emergent properties following brain injury: The claustrum as a major component of a pathway that influence nociceptive thresholds to foot shock in rats. Perceptual & Motor Skills, 85(2), 387-398. https://doi.org/10.2466/pms.1997.85.2.387
Tupper, K. W., Wood, E., Yensen, R., Johnson, M. W. (2015). Psychedelic medicine: A re-emerging therapeutic paradigm. CMAJ, 187(14), 1054-1059. https://doi.org/10.1503/cmaj.141124
U.S. National Library of Medicine (2021). ClinicalTrials: A multi-site phase 3 study of MDMA-assisted psychotherapy for PTSD. Retrieved from https://clinicaltrials.gov/ct2/show/NCT03537014 (accessed May 6, 2021).
Wagner, M. T., Mithoefer, M. C., Mithoefer, A. T., MacAulay, R. K., Jerome, L., Yazar-Kiosinski, B., Doblin, R. (2017). Therapeutic effect of increased openness: Investigating mechanism of action in MDMA-assisted psychotherapy. Journal of Psychopharmacology, 31(8), 967-974. https://doi.org/10.1177/0269881117711712
White, S. F., Costanzo, M. E., Blair, J. R., Roy, M. J. (2015). PTSD symptom severity is associated with increased recruitment of top-down attentional control in a trauma-exposed sample. NeuroImage: Clinical, 7, 19-27. https://doi.org/10.1016/j.nicl.2014.11.012
Williams, M. T., Davis, A. K., Xin, Y., Sepeda, N. D., Grigas, P. C., Sinnott, S., Haeny, A. M. (2020). People of color in North America report improvements in racial trauma and mental health symptoms following psychedelic experiences. Drugs: Education, Prevention & Policy, 28(3), 215-226. https://doi.org/10.1080/09687637.2020.1854688