Low Doses of LSD Acutely Increase BDNF Blood Plasma Levels in Healthy Volunteers

Despite preclinical evidence for psychedelic-induced neuroplasticity, confirmation in humans is grossly lacking. Given the increased interest in using low doses of psychedelics for psychiatric indications and the importance of neuroplasticity in the therapeutic response, this placebo-controlled within-subject study investigated the effect of single low doses of LSD (5, 10, and 20 μg) on circulating BDNF levels in healthy volunteers. Blood samples were collected every 2 h over 6 h, and BDNF levels were determined afterward in blood plasma using ELISA. The findings demonstrated an increase in BDNF blood plasma levels at 4 h (5 μg) and 6 h (5 and 20 μg) compared to that for the placebo. The finding that LSD acutely increases BDNF levels warrants studies in patient populations. P reclinical research has demonstrated that psychedelic substances, including 2,5-dimethoxy-4-iodoamphetamine (DOI), lysergic acid diethylamide (LSD), N,N-dimethyltrypt-amine (DMT), and psilocybin, as well as alkaloids present in ayahuasca (harmine, tetrahydroharmine, and harmaline) affect neuroplasticity after acute and chronic administration. 1−5 Catlow and colleagues, for example, demonstrated the increased formation of neurons (neurogenesis) in mice' dentate gyrus after an average psilocybin dose of 3.5 μg/35 g bodyweight (intraperitoneal (i.p.)), while this was slightly decreased after a dose of 35 μg/35 g (psilocybin/body-weight). 6 Interestingly, when repeatedly given i.p. psilocybin four times interspersed with 1 week, a higher dose of 52 μg/35 g (psilocybin/bodyweight) increased neuroplasticity. 2 Chronic administration in rats of twice the ritualistic dose of ayahuasca (150 mL/70 kg bodyweight containing 0.26 mg/kg DMT) for 28 days resulted in increased in brain-derived neurotrophic factor (BDNF) levels in the hippocampus of the female rats, compared to that in control animals. 7 A recent in vitro study in cultured cortical neurons of animals showed increased formation of new neurites, as expressed by the number of dendritic branches, the total length of the arbors, and formation of synapses, after extended (24 h) treatment with a range of psychedelics like DOI, LSD, and DMT. 1 While these effects were similar across psychedelic classes and the dissociative ketamine, LSD was the most potent, as shown via neuritogenesis assay. 1 Also in cultured human cortical neurons, the neuro-regenerative effects of DMT 8 and modulation of proteins involved in dendritic spine formation by 5-MeO-DMT have been shown. 9