Renewed interest in psychedelics as potentially useful therapeutic agents

June 2018
NDRI Adjunct Research Fellow Dr Stephen Bright shares his views about psychedelic research programs that have been initiated by several prestigious international institutions, and asks whether Australia risks being left behind if it doesn't follow suit.
  1. Adjunct Research Fellow, National Drug Research Institute, Curtin University
  2. Senior Lecturer (Addiction), Edith Cowan University
  3. Vice President, Psychedelic Research in Science & Medicine

We are in the midst of an international psychedelic science renaissance. Prestigious institutions such as Imperial College, UCLA, New York University and Johns Hopkins Medical School have initiated robust psychedelic research programs (Bright, Williams, & Caldicot, 2017). The classic psychedelic drugs being investigated include Lysergic Acid Diethylamide (LSD), psilocybin (the psychoactive chemical in ‘magic mushrooms’) and Dimethyltryptamine (DMT). This research is providing increasing evidence that psychedelics might be powerful therapeutic tools that could be harnessed in the treatment of depression, anxiety, trauma and substance use disorders (for review, see Bright & Williams, 2018; Nichols, 2016).

The investigation of these drugs as potentially useful therapeutic agents challenges the traditional framing of these substances, which has focussed on their potential risks and adverse consequences while overlooking their therapeutic potential. However, Australia has yet to join the international scientific community in exploring the clinical utility of these substances, largely due to the stigma still associated with them as illicit drugs (Puspanathan, 2017; Strauss, Bright, & Williams, 2016).

An epidemiological study involving 191,832 adult US citizens found that when controlling for polydrug use, people with a lifetime history of psychedelic use were less likely to have had suicidal ideation in the past 12 months and had lower levels of past month psychological distress than those who had not used psychedelics (Hendricks, Thorne, Clark, Coombs, & Johnson, 2015). A comprehensive review of the psychopharmacology of psychedelics by Nichols (2016) found only anecdotal evidence suggesting a link between psychedelic use and psychotic disorders. Further, the notion of people having “flashbacks” had been exaggerated, with Nichols (2016) stating, “the clinical relevance of flashback phenomena [such] as a post-hallucinogenic psychiatric disorder has to be disputed” (p.278). Nonetheless, some harms, and even deaths, have occurred because of misadventure associated with the recreational use of psychedelics; however, there have been no reported overdoses from the classic psychedelics, though overdoses have been reported from new psychoactive drugs that have psychedelic properties (Nichols, 2016). Certainly, we should continue to caution people with a predisposition to psychotic disorders against the possible mental health effects of using psychedelic drugs; however, the degree to which psychedelic drugs induce mental illness has been overestimated (Nichols, 2016).

Recent research has shown that with appropriate screening to avoid any adverse consequences, psychedelic drugs can be safety administered in a clinical setting to reduce psychological distress or even provide a cure for some patients (for review, see Bright & Williams, 2018; Nichols, 2016). Compared with psychedelic-assisted psychotherapy being provided in the 1960’s, contemporary therapies involve a large focus on preparation, to ensure that patients have adequate coping strategies for engaging in the psychedelic experience, and integration, so that patients are able to apply their experience to daily life (for review, see Bright & Williams, 2018). The administration of psychedelics occurs on only two or three occasions, during which time patients listen to carefully selected music while being supported by a trained co-therapist team. The therapeutic role of the music has been found to be complex, with qualitative research indicating that the tracks reported to be more challenging for patients are also the most therapeutic (Kaelen et al., 2018). 

Among people receiving palliative care, psychedelic-assisted psychotherapy has been found to be effective in reducing anxiety and depression, while improving quality of life and interactions with significant others (Gasser et al., 2014; Griffiths et al., 2016; Ross et al., 2016). There is also preliminary evidence that psychedelic-assisted psychotherapy might be effective in the treatment of chronic depression (Carhart-Harris et al., 2016) and substance use disorders (Bogenschutz et al., 2015; Johnson, Garcia-Romeu, & Griffiths, 2017). The research teams who completed these studies are now conducting large randomised controlled trials that aim to determine the efficacy psychedelic-assisted psychotherapy for these conditions.

While not a prototypical psychedelic, 3,4-methelynedioxymethamphetamine (MDMA) also has a history of use in psychotherapy. However, in 1986 it was banned in the USA despite recommendations from a federal inquiry recommending it be classified as a medicine (Rosenbaum, 2002). Since then, six Phase II clinical studies of MDMA-assisted psychotherapy for Post-traumatic Stress Disorder (PTSD) have been completed, with the pooled data showing that 66% of patients who received MDMA no longer met diagnostic criteria for PTSD at 12-month follow up (Feduccia, Holland, & Mithoefer, 2018). This data was presented to the USA’s Food and Drug Administration (FDA), who have given Breakthrough Designation for a Phase III international multisite study that includes a compassionate access scheme (Feduccia et al., 2018). This trial will commence in the USA, Canada and Israel within the next few months and will likely see MDMA an FDA-approved medicine before 2021.

By not joining the international scientific community in initiating a psychedelic science research program, Australia risks being left behind as these drugs become prescription medicines. Should MDMA become an FDA-approved medicine, it is unlikely that approval to use MDMA would be granted by the TGA here in Australia since we will not have adequately trained personnel or have demonstrated that our existing healthcare infrastructure is adequate to provide these treatments. It is in this environment there is concern that some people could potentially place themselves at-risk by taking illicit drugs in uncontrolled settings in an effort to self-medicate as publicity of the success of international trials of psychedelics as therapeutic agents continues to appear the Australian media.

References

Bogenschutz, M. P., Forcehimes, A. A., Pommy, J. A., Wilcox, C. E., Barbosa, P., & Strassman, R. J. (2015). Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study. Journal of Psychopharmacology, 29, 289-299. doi:10.1177/0269881114565144

Bright, S. J., & Williams, M. (2018). Should Australian Psychology Consider Enhancing Psychotherapeutic Interventions with Psychedelic Drugs? A Call for Research. Australian Psychologist. doi:10.1111/ap.12345

Bright, S. J., Williams, M., & Caldicott, D. (2017). Should addiction researchers be interested in psychedelic science? Drug and Alcohol Review, 36, 285-287. doi:10.1111/dar.12544

Carhart-Harris, R. L., Bolstridge, M., Rucker, J., Day, C. M., Erritoze, D., Kaelen, M., . . . Nutt, D. (2016). Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Lancet Psychiatry, 3, 619–627. doi:10.1016/S2215-0366(16)30065-7

Feduccia, A. A., Holland, J., & Mithoefer, M. C. (2018). Progress and promise for the MDMA drug development program. Psychopharmacology, 235, 561-571. doi:10.1007/s00213-017-4779-2

Gasser, P., Holstein, D., Michel, Y., Doblin, R., Yazar-Klosinski, B., Passie, T., & Brenneisen, R. (2014). Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases. The Journal of Nervous and Mental Disease, 202, 513-520. doi:10.1097/NMD.0000000000000113

Griffiths, R. R., Johnson, M. W., Carducci, M. A., Umbricht, A., Richards, W. A., Richards, B. D., . . . 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, 1181-1197. doi:10.1177/0269881116675513

Hendricks, P. S., Thorne, C. B., Clark, C. B., Coombs, D. W., & Johnson, M. W. (2015). Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population. Journal of Psychopharmacology, 29, 280-288. doi:10.1177/0269881114565653

Johnson, M. W., Garcia-Romeu, A., & Griffiths, R. R. (2017). Long-term follow-up of psilocybin-facilitated smoking cessation. The American Journal of Drug and Alcohol Abuse, 43, 55-60. doi:10.3109/00952990.2016.1170135

Kaelen, M., Giribaldi, B., Raine, J., Evans, L., Timmerman-Slater, C., Rodriguez, N., . . . Carhart-Harris, R. (2018). The hidden therapist: Evidence for a central role of music in psychedelic therapy. Psychopharmacology. doi:10.1007/s00213-017-4820-5

Nichols, D. E. (2016). Psychedelics. Pharmacological Reviews, 68, 264-355.

Puspanathan, P. (2017). Psychedelic research in Australia: Breaking through the stigma. The Australian and New Zealand Journal of Psychiatry, 51, 940-941. doi:10.1177/0004867417701580

Rosenbaum, M. (2002). Ecstasy: America's new 'reefer madness'. Journal of Psychoactive Drugs, 34, 137-142.

Ross, S., Bossis, A., Agin-Liebes, G., Malone, T., Cohen, B., Mennenga, S. E., . . . Schmidt, B. L. (2016). Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. Journal of Psychopharmacology, 30(12), 1165-1180. doi:10.1177/0269881116675512

Strauss, N., Bright, S. J., & Williams, M. (2016). Australia should be initiating a psychedelic research program: What are the barriers? Australian and New Zealand Journal of Psychiatry, 50, 1036-1037. doi:10.1177/0004867416670520