In March 2019, researchers at Johns Hopkins School of Medicine published a paper in The American Journal of Drug and Alcohol Abuse examining the improvements in anxiety and depression study participants experienced using 5-MeO-DMT (N, N-dimethyl-5-methoxytryptamine) in a naturalistic group setting.1 These improvements were an unexpected result of a previous web-based epidemiological study survey of 515 people who used 5-MeO-DMT.2
The data from this previous study revealed the majority of survey respondents who had psychiatric disorders and used 5-MeO-DMT reported improvements in their symptoms.2 Specifically, 77% had improvement in depressive symptoms, and 69% experienced improved anxiety symptoms. Also, 79% reported improvement in their post-traumatic stress disorder (PTSD) symptoms, 66% in alcoholism symptoms, and 60% saw improvement in their drug use disorder symptoms.
The current study examined the improvements to depression and anxiety symptoms from 5-MeO-DMT users in a structured and controlled group setting to understand more about the experiences of the users. The group setting included structured procedures for dosing and administration of 5-MeO-DMT as well as other procedures used in clinical trials of hallucinogens like preparation for, and support during and after administration sessions.1
Significant Improvement in Anxiety and Depression
The current study examined the self-reported improvement in anxiety and depression of 362 survey respondents (55% male).1 Of the total respondents, 41% were diagnosed with depression and 48% were diagnosed with anxiety. Eighty percent of those diagnosed with depression reported improvement in depressive symptoms. Of those diagnosed with anxiety, 79% reported improvement.
The researchers also observed from the data that, “Improvement in depression/anxiety conditions were associated with greater intensity of mystical experiences and higher ratings of the spiritual significance and personal meaning of the 5-MeO-DMT experience.” Also, there was no association between the intensity of any challenging physical or psychological effects of the 5-MeO-DMT experience and improvements in depression or anxiety.
Of particular interest when it comes to 5-MeO-DMT in therapeutic applications is its fast action and short duration compared to other psychedelics. Currently, researchers are having success in treating depression with psilocybin-assisted therapy (PcbAP). However, these treatment sessions can last 7 to 8 hours because of the long-lasting duration of psilocybin in the body. In contrast, “Because 5-MeO-DMT is short-acting and lasts approximately 30-90 minutes, it could be much easier to use as an adjunct to therapy because current therapies usually involve a 60 — 90-minute session,” says Alan K. Davis, Ph.D., a postdoctoral research fellow at the Johns Hopkins University School of Medicine.
The Importance of the Entourage Effect
The compound 5-MeO-DMT is a naturally-occurring and found in a variety of plants and animals. Some of the highest concentrations are in the venom of the toad Bufo alvarius.2 Historically, synthetic, toad- and plant-based sources of 5-MeO-DMT have been used for recreational and spiritual purposes. It is important to note that both of the studies discussed above used synthetic 5-MeO-DMT made in the laboratory, not an extract of compounds obtained from plant or animal sources.
Figure 1 shows the chemical structure of 5-MeO-DMT and two other toad venoms, bufotenin and bufotenidine. The differences may appear subtle from a chemical standpoint. But in the body, they can cause substantially different effects. For example, bufotenin is a known psychoactive molecule while bufotenidine causes paralysis.
In the world of magic mushrooms and cannabis, this synergistic interaction between compounds is called the entourage effect.
People who ingest frog venom secretions receive a cocktail of potentially psychoactive compounds, not just 5-MeO-DMT. There is no research being done on the effects and receptor binding interactions of 5-MeO-DMT, bufotenin, and bufotenidine and how these and other compounds in toad venoms interact together, resulting in overall psychoactive experience for the user.
Figure 1: The chemical structures of three toad venom compounds; 5-MeO-DMT, bufotenin, and bufotenidine illustrating their similarities and differences.
Conclusion
Through scientific studies like these, researchers are coming to understand the enormous benefits of psychedelics for treating mental conditions. However, research focusing on single synthetically-derived compounds like 5-MeO-DMT does not take into consideration the entourage effect. The positive benefits observed with single chemicals are encouraging and important. But formulations containing different types and amounts of toad venoms, for example, may provide even more benefits for users for an even wider variety of conditions.
Barbara E. Bauer, MS
Barb is the former Editor and one of the founders of Psychedelic Science Review. She is currently a contributing writer. Her goal is making accurate and concise psychedelic science research assessable so that researchers and private citizens can make informed decisions.