Amid the worldwide opioid crisis, the fight to combat opioid use disorder (OUD) has reached a strange crossroads. On one hand, healthcare practitioners are right to celebrate the advances brought on by medication-assisted therapy (MAT). Indeed, buprenorphine/Suboxone treatments have proven to be a safer and more effective method to treat OUD than predecessor approaches, and certainly more effective than utilizing behavioral interventions alone. On the other hand, the aforementioned MAT drugs come with inherent risks, ranging from prolonged withdrawal periods to plentiful side effects. A thorough review of the controversial  role of buprenorphine in combating opioid addiction can be found here.1

That being said, a need for new effective treatments is evident. While current MAT methods ought to be explored further with a heavy consideration of systematic factors involved, a new pharmacologic component may revolutionize addiction treatment.

Entheon Biomedical DMT OUD addiction opioid epidemic psychedelic drug therapy

 A Novel Approach: Using Dimethyltryptamine (DMT) for Addiction Treatment  

Timothy Ko, CEO of Entheon Biomedical, believes the answer resides within psychedelic-assisted psychotherapy – one of the emerging methods showing promise in treating SUD.2 Entheon Biomedical is a Canadian research and development company aiming to develop and commercialize a portfolio of psychedelic therapeutic products for the treatment of addictive disorders, such as OUD.

Psychedelics are a class of drugs that alter the user’s perception and mood. Despite the extensive misinformation campaigns of the prohibition era, research has established that these drugs are generally considered non-addictive and physiologically safe3. While this class includes mescaline, LSD, and psilocybin among other compounds3, Entheon Biomedical’s initial target is to utilize the powerful compound N,N-dimethyltryptamine (DMT) as an adjunct to psychotherapy. DMT is the active ingredient in the traditional Amazonian hallucinogenic brew, ayahuasca, which has been used as a therapeutic tool by indigenous cultures for thousands of years. 

The company’s research is largely spearheaded by a handful of scientific advisers, including Robin Carhart-Harris, Ph.D., who heads the Psychedelic Research Group within the Centre of Psychiatry at Imperial College London, and Matthew W. Johnson, Ph.D., a Professor of Psychiatry and Behavioral Sciences at John Hopkins.

Read “Can Psychedelic Therapy Ease the Socioeconomic Burden of Addiction?”

Entheon Biomedical DMT OUD addiction opioid epidemic psychedelic drug therapy

The Powerful Backstory and Inspiration Behind Entheon Biomedical          

Ko started Entheon Biomedical following the death of his brother, who struggled with addiction to opioids among other substances. 

“Underpinning this addiction was a traumatic botched surgery he had as a teenager that resulted in him not being able to integrate into society for many years,” said Ko.

 During that time, his brother was secluded in Ko’s family home for a number of years and started using drugs to cope with his depression.

         Over the course of two decades, he watched his brother undergo various interventions, including MAT. “He’d previously been in residential programs and tried medication-assisted therapy, such as methadone,” said Ko. His brother tried many different medications in pursuit of symptom management, including antidepressants, anxiolytics, antipsychotics, mood stabilizers, and lithium. When such methods did not work, his brother tried 12-step abstinence programs, electroconvulsive shock therapy, and more.

“In AA type programs, there is a requirement that the individual be honest with themselves about their experience so that they can recover,” said Ko. “They can work through resentment and shame to undo some of the fundamentally damaging behaviors they have.” Despite collective professional efforts to help him, Ko says nothing was able “to facilitate that profound internal shift” in the psychological issues underpinning his brother’s substance use. He ultimately succumbed to his addiction in March of last year.

Entheon Biomedical DMT OUD addiction opioid epidemic psychedelic drug therapy

Neuroplasticity & The Default Mode Network: The Science of Psychedelic Drugs

According to Ko, psychedelic usage can open up components of openness and self-transcendence. “From a neuro plasticity perspective, it allows the user to face more difficult elements of thinking.”

Ko explained that the default mode network (DMN), a series of neuropathways, has a “more prominent and governing role in premeditation and obsession” in those struggling with all types of addiction, not just OUD. “Psychedelics are known to change one’s relationship to the default mode network so that it increases brain entropy and allows for more connectivity,” said Ko.

Indeed, Robin Carhart-Harris’s 2014 paper The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs confirms these notions of DMN-impacting, entropy increasing, connectivity inducing psychedelic states. The paper states the DMN is the “highest level of a functional hierarchy” and “serves as a central orchestrator or conductor of global brain function.”4 The paper goes on to state the DMN is the “physical counterpart of the narrative-self or ego.”4

If the DMN is viewed as the ego, and psychedelics change one’s relationship with their DMN, then perhaps the psychedelic experience allows the user to recontextualize narratives of themselves, their lives, and their vices. As a metaphor, one could say the experience “shakes the snow globe” of previously routine thoughts and behaviors, allowing new behaviors to take place. The paper describes this “shaking” more clearly:

“…It is the ability of psychedelics to disrupt stereotyped patterns of thought and behavior by disintegrating the patterns of activity upon which they rest that accounts for their therapeutic potential.”4

The logic behind Entheon Biomedical’s faith in psychedelics to treat SUD when combined with therapy is worded nicely in the conclusion of Harris’s paper:

 

“Thus, in summary, it is hypothesized that there is a basic mechanism by which psychedelics can be helpful in psychiatry, whether they be used to treat depression, OCD (Moreno et al., 2006) or addiction (Krebs and Johansen, 2012). Specifically, it is proposed that psychedelics work by dismantling reinforced patterns of negative thought and behavior by breaking down the stable spatiotemporal patterns of brain activity upon which they rest.”4

Exploring & Expanding The  Therapeutic Models Used to Treat Addiction

Matthew W. Johnson is consulting the therapeutic models being investigated at Entheon. The number of hours before and after the DMT experience, Ko explained, helps the therapist and patient establish trust, understanding, and the intention of the sessions. The outline of the client’s issues they would like to work through becomes the purpose, or “theme,” of the psychedelic trip. “Therapy with the psychedelic experience will embolden the person to make those structural changes towards how they interact with life, their relationships, etc.,” said Ko.

“Also, that person will bear witness to some very intense and fear-inducing visuals and feelings,” said Ko. “So, therapy is a way people can navigate through that.” This is explicitly stated on the product’s general label – this is not a therapy unto itself, but an adjunct to supplemental therapeutics.

DMT vs Psilocybin: Current Applications & Future Possibilities

While Entheon Biomedical may look into psilocybin in the future, they believe the qualities of DMT are more ideal for treating substance abuse disorder. “DMT is such a promising molecule for some of the reasons people think its unwieldy and difficult to utilize, such as its short acting nature and intensity,” said Ko. “But those same properties allow us to modulate that experience at lower doses.”

According to Ko, where the effects of psilocybin might last 4-8 hours, continuously administered DMT “can have a short and profound effect, all the way down to a single dose from 15-20 minutes, to 1.5-2.5 hours, which is where we’re planning to extend it.”

Being an intense drug, this shortness of duration also serves as a way to minimize negative experiences with DMT. “Psychedelic molecules have profound and overwhelming effects, and when served to the greater half of the population, there is bound to be the occasional negative experience,” said Ko. “But with DMT being so short acting, if that situation were to occur, we can discontinue the administration of the drug and get that person quickly back to baseline.”

Entheon Biomedical DMT OUD addiction opioid epidemic psychedelic drug therapy

Psychedelic Medicine for Addiction is Making Headlines in a Big Way

Though in its infancy, the premise of using psychedelics in a therapeutic context has made headlines in recent years. For example, Matthew Johnson’s 2014 pilot study concluded that psilocybin has significant potential in helping cigarette smokers quit their habit.5 Here, 15 nicotine-dependent participants underwent several cognitive behavioral therapy sessions following two or three doses of psilocybin. An “open label study,” there was no placebo and it was not randomized (one could imagine the difficulties of conducting a double-blind placebo with psychedelics). Participants were to stop smoking before partaking in the sessions. Their carbon monoxide levels were measured at several intervals to ensure compliance. Six months later, 80 percent of participants were still abstinent from smoking. At the one-year mark, this fell to 67 percent.

Many studies arrived at similar conclusions. A 2019 study found LSD was effective in reducing problematic alcohol use.6 Likewise, a 2018 study found psilocybin-assisted therapy to reduce alcohol consumption in alignment with participant goals, respectively.6 Finally, a 2013 study found ayahuasca, a psychotropic brew containing DMT, to be “associated with statistically significant improvements in several factors related to problematic substance use among a rural aboriginal population.”7 Psilocybin was also found to reduce anxiety and depression in patients with life-threatening cancer.11

While these studies vary in what specific psychedelic they investigate, Ko says many of these drugs have similar functions.

“Psychedelic tryptamines differ mildly in terms of duration and physiological effects, like dieting a mushroom might create stomach rumbling,” said Ko. “But they all bind to 5HT2A receptors in the brain and body. They all sort of switch off that default mode network, increase entropy, openness – they all help the patient be both subject and observer to work with themselves to break down the partitions of compartmentalized aspects of the self.”

Entheon Biomedical DMT OUD addiction opioid epidemic psychedelic drug therapy

The Current Status for Entheon Biomedical & A Look at the Road Ahead

While Entheon Biomedical eventually plans to enter proprietary combinations of psychedelic molecules into the FDA, EMA, and Health Canada approval model, the company is still in its beginning stages.

They are currently preparing to initiate preclinical trials with universities and contract research organizations to yield baseline toxicology data. Animal behavioral trials are expected to follow shortly thereafter to determine if the administration of their formulations yield reductions in drug seeking behavior and increased sociability in test animals.9

If the animal studies yield successful results, “Entheon Biomedical would then commit to one of the licensed research organizations it is in dialogue with to begin the work of carrying out human trials in a strict academic environment, yielding data to be put toward its FDA, EMA and Canada Health approval applications.”9

Even if psychedelic-assisted treatment for SUD has a long way to go before being fully implemented, it is possible that it will become a reality relatively soon. As we saw in the 2019 FDA approval of esketamine (a potent form of the dissociative drug ketamine) for treatment-resistant depression10, or with Oakland’s decriminalization of psilocybin mushrooms, a drug’s illicit status does not necessarily render it obsolete in a clinical context. Likewise, it does not render it obsolete in the court of public opinion.

Entheon Biomedical DMT OUD addiction opioid epidemic psychedelic drug therapy

Supporting the Psychedelic Renaissance

In the meantime, those interested in psychedelic-assisted therapy have a handful of ventures they can look into.

“There are other ways to support non-profit psychedelic research, like the McKenna academy,” said Ko. “Which is for the preservation of the Amazon jungle that psychedelic researchers owe a lot to.”

Here, Ko is referring to the indigenous Amazonian cultures who’ve long used psychedelic plants as both religious sacraments and healing tools. “Without the work of psychedelic forebears, none of this would be possible,” said Ko. Entheon Biomedical has donated to the McKenna academy, headed by Dennis McKenna, an ethnopharmacologist and scientific adviser to Entheon.

Ko also suggests looking into COMPASS Pathways, a company famously proposing the efficacy of psychedelics in the treatment of depression. Of course, nonprofit research and educational organizations such as the Multidisciplinary Association of Psychedelics (MAPS) and the Heffter Research Institute are some of the most influential groups in psychedelic research.

Want to support the psychedelic renaissance? Read “Microdose Presents: MicroDonations” to learn how you can contribute!

Entheon Biomedical DMT OUD addiction opioid epidemic psychedelic drug therapy

Closing thoughts on psychedelic-assisted psychotherapy for OUD treatment.

As Ko would attest to, psychedelic therapy and conventional MAT are not in competition with each other. In fact, they are in collaboration. Both view drugs as an adjunct to quality therapeutic relationships (rapport, unconditional positive regard, etc.). Likewise, some approaches may be more tailored to an individual’s circumstances than others. The clinical community is not in the pursuit of discovering panaceas, but rather a pursuit of discovery itself.

 

References

1: Dubey, G. (2020). The Controversial Role of Buprenorphine in Combating Opioid Addiction, According to Science. Evolve Indy. https://evolveindy.com/the-controversial-role-of-buprenorphine-in-combating-opioid-addiction-according-to-science/

2: Bas T.H. de Veen, Arnt F.A. Schellekens, Michel M.M. Verheij & Judith R. Homberg. (2017). Psilocybin for treating substance use disorders?, Expert Review of Neurotherapeutics, 17:2, 203-212, https://doi.org/10.1080/14737175.2016.1220834

3: Nichols D. E. (2016). Psychedelics. Pharmacological reviews, 68(2), 264–355. https://doi.org/10.1124/pr.115.011478

4: Carhart-Harris, R. L., Leech, R., Hellyer, P. J., Shanahan, M., Feilding, A., Tagliazucchi, E., Chialvo, D.R., Nutt, D. (2014). The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs. Frontiers in Human Neuroscience, 8. https://doi.org/10.3389/fnhum.2014.00020

5: Johnson, M. W., Garcia-Romeu, A., Cosimano, M. P., & Griffiths, R. R. (2014). Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. Journal of psychopharmacology (Oxford, England), 28(11), 983–992. https://doi.org/10.1177/0269881114548296

6: Garcia-Romeu, A., Davis, A. K., Erowid, F., Erowid, E., Griffiths, R. R., & Johnson, M. W. (2019). Cessation and reduction in alcohol consumption and misuse after psychedelic use. Journal of psychopharmacology (Oxford, England), 33(9), 1088–1101. https://doi.org/10.1177/0269881119845793

(7) 19: Bogenschutz, M. P., Podrebarac, S. K., Duane, J. H., Amegadzie, S. S., Malone, T. C., Owens, L. T., Ross, S., & Mennenga, S. E. (2018). Clinical Interpretations of Patient Experience in a Trial of Psilocybin-Assisted Psychotherapy for Alcohol Use Disorder. Frontiers in pharmacology, 9, 100. https://doi.org/10.3389/fphar.2018.00100

(8) 20: Thomas, G., Lucas, P., Capler, N. R., Tupper, K. W., & Martin, G. (2013). Ayahuasca-assisted therapy for addiction: results from a preliminary observational study in Canada. Current drug abuse reviews, 6(1), 30–42. https://doi.org/10.2174/15733998113099990003

(9) 21: Entheon Biomedical. (2020). https://entheonbiomedical.com/solution

(10) 22: Minkove, J.F. (2019). Esketamine: A New Approach for Patients with Treatment-Resistant Depression. Hopkins Medicine. https://www.hopkinsmedicine.org/news/articles/esketamine-a-new-approach-for-patients-with-treatment-resistant-depression

(11) 23: 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 (Oxford, England), 30(12), 1181–1197. https://doi.org/10.1177/0269881116675513