Ayahuasca reduces pain in mice without detectable toxic effects

A study on mice has revealed that ayahuasca acts as a potent analgesic without causing any detectable toxic effects. This analgesic property is partly due to harmine, a significant component of ayahuasca. The findings were published in the Journal of Ethnopharmacology.

Ayahuasca is a traditional South American brew used for centuries by indigenous tribes for spiritual and medicinal purposes. It is made from the Banisteriopsis caapi vine and the Psychotria viridis shrub, which contain harmala alkaloids and the psychoactive compound N,N-Dimethyltryptamine (DMT), respectively. When consumed, ayahuasca induces altered states of consciousness, which often include visions, introspection, and emotional revelations.

In recent years, ayahuasca has gained attention in the U.S. and Europe for its potential therapeutic benefits in treating mental health disorders such as depression, anxiety, and PTSD. However, its use is controversial due to its psychoactive properties and associated risks.

One of the key ingredients of ayahuasca is the substance called harmine, one of the harmala alkaloids. Harmine prevents the breakdown of DMT, of the neurotransmitter serotonin, and of some other neurotransmitters. This effect allows DMT to exert its psychedelic effects in the brain, contributing to the unique experiences associated with ayahuasca consumption.

Study author Pedro Santana Sales Luria and his colleagues noted that there is anecdotal evidence that, aside from the psychedelic effects, ayahuasca also has pain-killing properties. However, it remains unclear whether these effects are a result of the subjective psychedelic experience or are independent of it. They conducted a study on mice to investigate this effect.

The study was conducted on 257 male mice aged 3-6 months and weighing 20-25 grams each, obtained from the animal facilities of the Gonçalo Moniz Institute in Brazil. The researcher kept the mice in individually ventilated cages at room temperature and with free access to food and water.

The researchers conducted experiments with different concentrations of ayahuasca (24, 120, 600, and 3000 μL/kg) and compared them to reference anti-inflammatory and analgesic drugs like morphine and dexamethasone. A control group received water instead. Pain was induced using methods such as formaldehyde or complete Freund’s adjuvant injections, hot water tail immersion, or applying pressure with thin nylon threads (Von Frey filaments). Complete Freund’s adjuvant, a mixture containing dead Mycobacterium tuberculosis bacteria, induces persistent inflammation when injected.

These researchers also examined the effects of repeated treatments with ayahuasca and harmine, either by exposing or ligating the sciatic nerve of the mice to induce pain. The treatments included different doses of ayahuasca, harmine, water (as a control), or gabapentin, a drug used to treat neuropathic pain. The researchers observed the mice’s behavior following these treatments.

Additionally, to identify mechanisms of action of ayahuasca and harmine, the researchers used drugs that block various neural pathways to see how these would alter ayahuasca’s impact. They also employed a technique called fos protein immunohistochemistry to analyze the brains of the mice, identifying the most active areas shortly before the animals were euthanized.

Results showed that ayahuasca in concentrations above 120 μL/kg created pain-killing effects. However, it did not prevent the swelling of paws of experimental mice after these were treated with complete Freund’s adjuvant. This indicated that ayahuasca effects pain, but not inflammation. Also, ayahuasca did not modify the mice’ pain threshold when the researchers dipped their tails in hot water.

In experiments involving nerve ligation, the most effective dose of ayahuasca was 600 μL/kg, with peak effects occurring 7 hours after treatment and lasting between 5 to 8 hours. Higher doses maintained their effects for up to 10 hours. In contrast, the effects of gabapentin peaked 2-3 hours after administration. Repeated daily doses of ayahuasca consistently reduced pain.

Further analysis showed that these effects are mediated by receptors in the brain responsive to GABA (gamma-aminobutyric acid) and serotonin, increasing activity in brain areas that modulate pain perception. Importantly, the study found no toxic effects from ayahuasca treatment.

“Daily treatments with ayahuasca or harmine completely abolished the nociceptive [pain] sensitization that characterizes experimental and clinical neuropathic pain. The antinociceptive [pain-killing] effects of ayahuasca seem to be at least partially mediated by descending pain inhibitory pathways and involve serotonergic and GABAA receptors. Ayahuasca showed a good safety profile when given repeatedly, inducing no detectable signs of systemic toxicity after 14 days of daily oral administrations twice a day,” the study authors concluded.

The study sheds light on potential use of ayahuasca and its components for treating pain. However, it should be noted that the study was conducted on mice. While mice and humans share many similarities, they are also very different species. Results on humans might not be the same.

The paper, “Ayahuasca and its major component harmine promote antinociceptive effects in mouse models of acute and chronic pain,” was authored by Pedro Santana Sales Lauria, Juliana de Medeiros Gomes, Lucas Silva Abreu, Rejane Conceiçao Santana, Victor Luiz Correia Nunes, Ricardo David Couto, Paulo Oliveira Colavolpe, Marcelo Sobral da Silva, Milena Botelho Pereira Soares, and Cristiane Flora Villarrea.