Psychedelics vs. Cannabis: Exploring the Clinical Landscape

This blog is the first of its kind in an ongoing evidence-based series comparing, contrasting and contemplating the world of psychedelic medicine and cannabis. You can learn more about this exciting series and the topics it will cover here.

The evolution and expansion of scientific research into illicit drugs like cannabis and magic mushrooms has dramatically shifted the public’s perception of them. While cannabis and hemp products become commonplace, novel research is increasingly validating the potential of psychedelic drugs for severe neurological and psychological disorders. Indeed, the evolving body of research behind both cannabis and psychedelics continues to impact society in big ways. From the groundbreaking clinical trials using psilocybin for end-of-life anxiety to the FDA’s recent approval of Epidiolex (the first CBD drug), this guide will explore the latest clinical research surrounding both psychedelic medicine and medical cannabis.

Our Understanding of Psychedelics & Serotonin Far Outweighs That of Cannabis 


While both medical cannabis and psychedelic medicine have both demonstrated value in the research setting, there are some marked differences between the two. Perhaps the most striking difference between the two is the fact that psychedelic drugs and the brain regions they act upon are much better researched and understood when compared to cannabis.


The traditional psychedelic compounds, like LSD and psilocybin, act primarily upon serotonin–the 5HT2a serotonin receptor to be exact. The body of research into the serotonin receptor system is much deeper than that of our endocannabinoid system–the receptor system cannabis primarily exerts its effects upon. Despite the fact several studies have established the role of endocannabinoid signaling in conditions like anxiety and depression1, it is not a part of the mainstream medical curriculum. This has significantly limited progress in this important field of research and severely limited the potential scope of cannabinoid therapeutics. Fortunately, this is not the case for psychedelic drugs and the scope of knowledge surrounding them.

cannabis psychedelics clinical landscape clinical trial drug development

The Current State of Psychedelic Research is Dynamic & Rapidly Evolving


The revival of psychedelic research during this modern renaissance has unearthed a mountain of evidence validating their immense therapeutic potential. Groundbreaking clinical trials demonstrating the efficacy of psilocybin in treating everything from end-of-life anxiety2 to addiction3 have dominated headlines—and rightly so. We are on the cusp of a truly remarkable undertaking where, as a society, we have the ability, through psychedelic medicine, to truly impart lasting positive impact on the global mental health crisis. By drawing on the early research from the 60’s and 70’s, the current state of psychedelic science is making massive strides in medical research. These promising trends are only projected to continue as research into these powerful compounds shift public perception and global drug policy.

cannabis psychedelics clinical landscape clinical trial drug development

The Complexity of Cannabinoid Research Is Inhibiting Translation into Effective Therapeutics  


Contrary to psychedelic science, our current paradigms for drug development cannot effectively accommodate for the complexity of cannabinoid pharmacology. While singular molecules like DMT or psilocybin have shown to be incredibly efficacious on their own (and outside of their plant-based context), the same cannot be said of the therapeutic efficacy of lone cannabinoids like THC or CBD. There major exception here, of course, is the clinical value of CBD isolate has for the treatment of severe childhood epilepsy. Indeed, the FDA’s approval of Epidiolex, the first CBD drug, reflects this clearly.4 Unfortunately, outside of this important yet limited clinical indication, the field of cannabinoid therapeutics does not have much to offer. While cannabis advocates far and wide claim the therapeutic powers of whole plant cannabis in the treatment of a variety of conditions, including cancer, there simply lacks clinical data to support this. As a clinical biologist and science writer, it is my hypothesis that modern pharmacopeia lacks novel and robust cannabinoid therapeutics due to our inability to understand the complex interactions between all the elements in whole plant cannabis—also called the “entourage effect”.

cannabis psychedelics clinical landscape clinical trial drug development

Unlocking The “Entourage Effect” May Spark a New Generation of Cannabinoid Therapies


The intricate and multidimensional “entourage effect” exhibited by cannabis, while thought to be responsible for its wide-ranging therapeutic effects, is simply too far outside our current “single-molecule” drug development paradigm. In a piece I recently published for Green Flower Media, I expanded upon this line of reasoning described it as the reason why cannabis seems to have “failed to deliver on its clinical promise.5 Indeed, expanding our current framework for understanding pharmacology to extend beyond the “single molecule” paradigm has the potential to park a whole new generation of cannabinoid therapeutics. Today, leading researchers and clinicians are using tools like artificial intelligence to unlock the mystery of the entourage effect that lies in complex cannabinoid signaling. It is entirely possible that advances in our understanding of cannabis and, perhaps more importantly, our internal endocannabinoid system can lead to a new generation of powerful new drugs. However, until then, drug development in the cannabinoid space has certainly taken a backseat to psychedelic medicine.

cannabis psychedelics clinical landscape clinical trial drug development

Looking Ahead to the Rapidly Evolving Clinical Landscape for Cannabis and Psychedelics


Currently, there are over 200 clinical trials exploring the therapeutic benefits of psychedelic compounds. While the pandemic has understandably limited the progress of these trials, many pioneers in the psychedelic space are rapidly positioning themselves for the next steps. On the contrary, there are currently only 2 medical marijuana clinical trials scheduled for 2020 (both of which have the current status of “recruiting”). As the clinical landscape for both these classes of drugs continues to expand, it’s clear that investor interest is currently drawn to the psychedelic sector—and quite heavily. While the exact details of the next blockbuster drug is still anyone’s guess, the evidence shows there is a high probability it will emerge from the psychedelic sector.

cannabis psychedelics clinical landscape clinical trial drug development

Works Cited


  1. Patel, S. & Hillard, C. J. Role of Endocannabinoid Signaling in Anxiety and Depression. Curr. Top. Behav. Neurosci. 1, (2009).
  2. Griffiths, R. R. et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J. Psychopharmacol. Oxf. Engl. 30, 1181–1197 (2016).
  3. Garcia-Romeu, A., Griffiths, R. R. & Johnson, M. W. Psilocybin-occasioned mystical experiences in the treatment of tobacco addiction. Curr. Drug Abuse Rev. 7, 157–164 (2014).
  4. Sekar, K. & Pack, A. Epidiolex as adjunct therapy for treatment of refractory epilepsy: a comprehensive review with a focus on adverse effects. F1000Research 8, (2019).
  5. Is Medical Cannabis Delivering Its Clinical Promise? | Green Flower News.
cannabis psychedelics clinical landscape clinical trial drug development

Gaurav Dubey

Gaurav Dubey

Gaurav Dubey is a dynamic clinical biologist, evidence-based branding professional and entrepreneur with a passion for scientific writing and traveling the world. He earned a dual bachelor’s degree in biology and philosophy from the University of Miami in 2011 and his Master’s in Biotechnology from Rush University Medical Center in 2015. Gaurav was recently published as lead author in the world's leading transplant journal, The Journal of Heart and Lung Transplantation, for a study investigating second-time lung re-transplantation. He is passionate about psychedelic medicine and recently accepted a position as content editor at Microdose, an opportunity he is very excited about. He is also the Founder & President of Karmik, LLC, an evidence-based branding firm for extraordinary life science brands.