Skin of the Toad: The Next Treatment for Depression?

Colorado River toads loved to swim in my pool and lay their eggs in the skimmer. Neighborhood dogs like to lick the backs of these toads; some of the smaller dogs did not survive the experience. These toads have parotoid glands near their eyes that produce two psychoactive chemicals: 5-methoxy-dimethyltryptamine (5-MeO-DMT) and bufotenin, named after the Bufo genus of toads.

Both chemicals belong to the family of hallucinogenic tryptamines that includes psilocybin. The toads produce bufotenin directly from the serotonin in the blood via one simple methylation step inside the gland. The 5-MeO-DMT is made via another simple enzymatic step from the bufotenine. The toads do not produce these chemicals for the amusement of humans; they utilize them as a defense against predators. Humans long ago discovered that the combination of these two psychoactive drugs produces euphoria, as well as visual and auditory hallucinations, due to stimulation of serotonin receptors. It is dangerous to lick the backs of these toads because the glands also release cardiac glycosides that are lethal.

Recent studies have reported success in using these two compounds together in psychedelic-assisted therapies for the treatment of suicidal ideation, cognitive impairment, depression, and PTSD. These are similar targets for psychedelic-assisted therapy using psilocybin. Studies have reported significant and very large self-reported reductions in anxiety as well. The participants rated the drug experience as one of the top five personally meaningful, spiritually significant, and psychologically insightful experiences of their entire lives.

A more recent study collected prospective clinical data at four time points (baseline/pre-treatment, one-, three-, and six-months after treatment) in a large population of Special Operations Forces Veterans. A program therapist explained the range of effects they might experience from ibogaine and 5-MeO-DMT. They were administered a single oral dose (10 mg/kg) of ibogaine and three incremental doses of 5-MeO-DMT starting at 5 mg, 15 mg, and 30 mg (for a total of 50mg) by inhalation. The attendees did not receive compensation.

The study reported significant improvements by participants across multiple domains of stress- and trauma-related concerns including both specific symptom constellations as well as associated features such as life satisfaction, psychological flexibility, meaning and purpose, and spirituality. Importantly, there were not only many healthy improvements in symptoms and various factors relating to mental health and well-being, but the benefits appeared after only three days of intervention. In contrast, currently available therapies require weeks to months to achieve any benefits.

This is the first study to report on the combined therapeutic effects of ibogaine and 5-MeO-DMT assisted therapy and to report on the potential benefits of psychedelic assisted treatment for patients suffering with PTSD using data that was collected in a longitudinal and prospective manner.

These findings are not dissimilar to those reported using other psychedelic medicines, with significant improvements noted soon after the therapy begins (hours to days) and sustained, durable benefits for months or more after a treatment.