Safety and tolerability of inhaled N,N-Dimethyltryptamine (BMND01 candidate): A phase I clinical trial.

Psychedelics are being increasingly examined for their therapeutic potential in mood disorders. While the acute effects of ayahuasca, psilocybin, and lysergic acid diethylamide (LSD) last over several hours, inhaled N,N-Dimethyltryptamine (DMT) effects last around 10 min, which might provide a cost- and time-effective alternative to the clinical application of oral psychedelics. We aimed at investigating the safety and tolerability of inhaled DMT (BMND01 candidate). We recruited 27 healthy volunteers to receive a first, lower dose and a second, higher dose (5/20 mg, 7.5/30 mg, 10/40 mg, 12.5/50 mg, or 15/60 mg) of inhaled DMT in an open-label, single-ascending, fixed-order, dose-response study design. We investigated subjective experiences (intensity, valence, and phenomenology), physiological effects (blood pressure, heart rate, respiratory rate, blood oxygen saturation, body temperature), biochemical markers (liver, kidney, and metabolic functions), and adverse events during the acute and post-acute effects of DMT. DMT dose-dependently increased intensity, valence and perceptual ratings. There was a mild, transient, and self-limited increase in blood pressure and heart rate. There were no changes in safety blood biomarkers and no serious adverse events. DMT dose-dependently enhanced subjective experiences and positive valence. Inhaled DMT might be an efficient, non-invasive, safe route of administration, which might simplify the clinical use of this substance. This is the first clinical trial to test the effects of inhaled DMT (BMND01 candidate).

Alterations of auditory sensory gating in mice with noise-induced tinnitus treated with nicotine and cannabis extract.

Tinnitus is a phantom sound perception affecting both auditory and limbic structures. The mechanisms of tinnitus remain unclear and it is debatable whether tinnitus alters attention to sound and the ability to inhibit repetitive sounds, a phenomenon also known as auditory gating. Here we investigate if noise exposure interferes with auditory gating and whether natural extracts of cannabis or nicotine could improve auditory pre-attentional processing in noise-exposed mice. We used 22 male C57BL/6J mice divided into noise-exposed (exposed to a 9-11 kHz narrow band noise for 1 h) and sham (no sound during noise exposure) groups. Hearing thresholds were measured using auditory brainstem responses, and tinnitus-like behavior was assessed using Gap prepulse inhibition of acoustic startle. After noise exposure, mice were implanted with multi-electrodes in the dorsal hippocampus to assess auditory event-related potentials in response to paired clicks. The results showed that mice with tinnitus-like behavior displayed auditory gating of repetitive clicks, but with larger amplitudes and longer latencies of the N40 component of the aERP waveform. The combination of cannabis extract and nicotine improved the auditory gating ratio in noise-exposed mice without permanent hearing threshold shifts. Lastly, the longer latency of the N40 component appears due to an increased sensitivity to cannabis extract in noise-exposed mice compared to sham mice. The study suggests that the altered central plasticity in tinnitus is more sensitive to the combined actions on the cholinergic and the endocannabinoid systems. Overall, the findings contribute to a better understanding of pharmacological modulation of auditory sensory gating.