Developing a Novel Psychedelic: Salvinorin A

A kappa-opioid receptor with psychedelic effects, this potential agent for treatment-resistant depression and other disorders will be paired with a digital therapeutic for maximum efficacy.

atai Life Sciences announced the launch of Revixia, a wholly owned subsidiary developing Salvinorin A (SalA) to treat a variety of mental health disorders. SalA, a unique non-nitrogenous agonist of the kappa-opioid receptor (KOR), is derived from Salvia divinorum.

SalA has a complex pharmacological profile. It is an atypical KOR agonist, and its mechanism of action (MoA) shows no interaction at the 5-HT2A serotonin receptor—the main molecular target for hallucinogens like psilocybin.

“Due to SalA’s short psychedelic effect, it will be an attractive option for those who would like psychedelic treatment but are unwilling or unable to participate in longer sessions,” said Glenn Short, CEO of Revixia. “The shorter experience will allow for more practical administration and monitoring, which may even make it possible to attend psychotherapy sessions on the same day.”1

Salvia divinorum has been traditionally used by the Mazatec people in Oaxaca, Mexico for a variety of illnesses, such as diarrhea, headaches, and rheumatism, as well as for palliative care. It also has potential use with treatment-resistant depression (TRD), substance use disorder (SUD), and pain.

Published reports suggest potential benefits of Salvia divinorum in the treatment of TRD. One doctor reported on 7 patients with TRD who described relief from depressive symptoms with triweekly oral consumption of salvia leaves. Several patients reported lasting benefits from their use of salvia, with significantly reduced scores on quantitative measures of depression. Patients also reported benefits like mood enhancement, increased feelings of relaxation, and increased self-awareness.2

"While SalA has until now been understudied, its unique MoA may allow for combination with SSRIs, potentially giving patients a better chance in beating depression," Srinivas Rao, CSO and cofounder of atai Life Sciences, said to the press. “We’re thrilled to be pursuing SalA and progressing research, as we strive for new treatments.”1

Revixia’s product will be paired with a digital therapeutic developed by atai company, Introspect Digital Therapeutics. The company hopes this pairing will streamline preparation, integration, and continued patient engagement.

“In exploring SalA, Revixia aims to develop a product with a differentiated pharmacological and treatment effect. Considering the significance of prior evidence in humans in parallel with the substantial unmet need in TRD, we believe Revixia has high commercial potential and an increased probability of success in the clinic,” Florian Brand, CEO and cofounder of atai Life Sciences, said. “SalA is a great product candidate that magnificently matches the criteria we strive for, with recognized synergies across the atai platform.”1

Clinical trials are expected to begin in the second half of 2022.

References

1. atai Life Sciences. atai launches Revixia Life Sciences to develop Salvinorin A for a variety of mental health conditions. News release. August 12, 2021. Accessed August 13, 2021. https://ir.atai.life/news-releases/news-release-details/atai-launches-revixia-life-sciences-develop-salvinorin-variety

2. Hanes KR. Salvia divinorum: clinical and research potential. Maps. 2003;13(1):18-20.