Should clinicians 'hop' on this psychedelic treatment?

In recent months, you may have heard various celebrities touting their experiences smoking psychedelic toad venom. For instance, HGTV star Christina Haack smoked it to combat her anxiety.

Most physicians aren’t in the habit of promoting psychedelic substances. But research exists suggesting potential clinical benefits of 5-MeO-DMT, the psychoactive substance found in toad venom.

Psychedelic use in context

Man has used psychedelics from plants and fungi for rituals and healing for hundreds of years. More recently, they’ve been used for self-medications targeting mental health.

Various classic psychedelics were researched in the psychiatry field before being placed on Schedule I of the UN Convention on Psychotropic Substances of 1971, which subsequently limited their ability to be researched or developed.

During the past 20 years, research on psychedelics has resumed, with encouraging data regarding psilocybin-assisted psychotherapy in individuals with depression and anxiety, as well as substance-use disorders. The effects of classic psychedelics (such as LSD) last about 12 hours, but shorter-acting ones such as dimethyltryptamine (DMT) may have therapeutic potential.

These shorter-acting forms could expand psychiatric treatment options and come at a lower cost, according to the authors of a review published in the Journal of Psychopharmacology.^[]

What is 5-MeO-DMT?

First synthesized in 1936, 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a short-acting serotonergic psychedelic that was later discovered in various plants. It’s also found in the fungi Amanita citrina and Amanita porphyria, along with the gland secretions of the Sonoran Desert toad, Incilius (Bufo) alvarius.

5-MeO-DMT is probably produced in humans naturally, and has been found in the blood, urine, and cerebrospinal fluid of some people. However, not all studies have confirmed these results, and the physiologic role of this compound remains to be elucidated.

Although indigenous people of South America have used 5-MeO-DMT-containing plants for millennia, the use of toad secretions is more recent and can be traced back to a pamphlet published by Albert Most in 1984.^[] It’s unlikely that indigenous South Americans used toad secretions, but instead developed snuffs and brews from 5-MeO-DMT plants.

5-MeO-DMT was rendered illegal by being listed on Schedule 1 of the US Controlled Substances Act in 2009. It’s also considered a controlled substance in the UK, Australia, New Zealand, and other countries. Intriguingly, recreational users have reported improvements in mental health after using 5-MeO-DMT.

Drug administration and metabolism

5-MeO-DMT is metabolized by the monoamine oxidase (MAO) enzymes of the gut and liver. Being orally inactive, it is usually smoked or vaped.

It can also be administered via intravenous, intramuscular, rectal, sublingual, or intranasal routes. These are rarely used, however, as smoking and vaping are easier and have become popularized.

Peak effect occurs in seconds and lasts between 15 and 20 minutes.

Acute adverse effects of 5-MeO-DMT intake include anxiety, confusion, fear, sadness, crying, paranoia, fatigue, trembling, vomiting, headache, nausea, chest/abdomen pressure, and loss of body perception.

Subacute effects entail flashbacks and reactivation of split-second flashes of light. Reactivations can occur days after initial intake and are more common with vaporization vs intramuscular administration.

“Of particular importance, the reactivation phenomenon has been reported primarily as a positive or neutral experience from large samples of recreational and ceremonial users,” wrote the authors of a review published in the Journal of Neurochemistry.^[] “Rare cases of psychosis have also been reported, sometimes when used in combination with other tryptamines.”

Synthetic variants

A synthetic tryptamine is 5-MeO-AMT, also known as alpha-O, as described by the National Drug Intelligence Center of the Department of Justice.^[] 5-MeO-AMT is smoked in powder form.

Other hallucinogen examples of tryptamines include AMT (alpha-methyltryptamine), 5-MeO-DIPT (5-methoxy-N,N-diisopropyltryptamine, also known as foxy), psilocybin, and psilocyn.

Adverse effects of 5-MeO-AMT can be physical and psychological, and include auditory disturbances/distortions, nausea/vomiting, and diarrhea. The hallucinations can be extremely frightening and lead to emotional distress. It can also lower inhibitions and lead to accidents, injuries, and high-risk sexual activity.

Therapeutic potential

The therapeutic potential for 5-MeO-DMT is intriguing, according to the authors of the review article published in the Journal of Psychopharmacology.

According to the authors, potential benefits over the classic psychedelics could include 5-MeO-DMT’s short duration of action, which may require less healthcare resource utilization, increasing access to treatment. The absence of visual effects, which could be distracting, might lead to higher rates of mystical experiences.

5-MeO-DMT “deserves further investigation as a putative rapid-acting antidepressant,” the authors conclude. “A key step will be establishing a pharmacokinetic profile and safety profile of 5-MeO-DMT in healthy volunteers in a controlled trial design.”