Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases

Abstract: A double-blind, randomized, active placebo-controlled pilot study was conducted to examine safety and efficacy of lysergic acid diethylamide (LSD)-assisted psychotherapy in 12 patients with anxiety associated with life-threatening diseases. Treatment included drug-free psychotherapy sessions supplemented by two LSD-assisted psychotherapy sessions 2 to 3 weeks apart. The participants received either 200 μg of LSD (n = 8) or 20 μg of LSD with an open-label crossover to 200 μg of LSD after the initial blinded treatment was unmasked (n = 4). At the 2-month follow-up, positive trends were found via the State-Trait Anxiety Inventory (STAI) in reductions in trait anxiety (p = 0.033) with an effect size of 1.1, and state anxiety was significantly reduced (p = 0.021) with an effect size of 1.2, with no acute or chronic adverse effects persisting beyond 1 day after treatment or treatment-related serious adverse events. STAI reductions were sustained for 12 months. These results indicate that when administered safely in a methodologically rigorous medically supervised psychotherapeutic setting, LSD can reduce anxiety, suggesting that larger controlled studies are warranted.

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LSD is a semisynthetic compound first synthesized in 1938 by Swiss chemist Albert Hofmann at Sandoz laboratories in Basel. Its psychoactive effects were discovered in 1943 (Hofmann, 1979). LSD was named Delysid and distributed by Sandoz as an investigational drug for psychiatric research (Hintzen and Passie, 2010). LSD-assisted psychotherapy was primarily explored for treating alcoholism, neurosis, and psychosomatic disorders (Abramson, 1967).

LSD in oral doses of more than 100 μg produces vivid psychosensory changes, including increased sensory perception, illusionary changes of perceived objects, synesthesia, and enhanced mental imagery. Affectivity is intensified. Thoughts are accelerated, with their scope usually broadened including new associations and modified interpretation and meanings of relationships and objects. Hypermnesia and enhanced memory processes typically occur. Ego identification is usually weakened. The general state of consciousness can be compared to a daydream, but with pronounced affectivity and enhanced production of inner stimuli (Grof, 1975; Hintzen and Passie, 2010). LSD has been described as a “non-specific amplifier of the unconscious” (Grof, 1975). These effects last for 6 to 9 hours and can be used to support and enhance psychotherapeutic processing.

LSD’s effects on brain functioning are complex and not fully understood. LSD influences diverse neurotransmitter systems (Nichols, 2004; Passie et al., 2008), but its psychosensory effects are mainly mediated by activation of the 5-HT2A receptors, with significant modulation by 5-HT2C and 5-HT1A receptors (Nichols, 2004; Vollenweider, 1998). No neuroimaging studies have been conducted with LSD, whereas neuroimaging studies with the LSD-related substances psilocybin (Carhart-Harris et al., 2012; Gouzoulis-Mayfrank et al., 1999; Vollenweider et al., 1997) and dimethyltryptamine (de Araujo et al., 2012; Riba et al., 2006) have yielded inconclusive results, presumably because of methodological challenges. The few congruent results throughout different studies are activation of the right hemisphere, altered thalamic functioning, and increased activity in paralimbic structures and the frontal cortex....[Full Article]