By Sandra Nomoto
Selective, Beneficial Effects on Mood and Cognition Observed
A study aimed to determine whether a low dose of Lysergic acid diethylamide (LSD) positively affects cognition and mood, and at which dose these effects occur. It was recently published in the journal European Neuropsychopharmacology.
Controlled research on the efficacy of microdosing is scarce. The primary objective of the study was to determine the minimal dose of LSD needed to affect mood and cognition. A placebo-controlled within-subject study with 24 healthy participants assessed the acute effects of three LSD doses (5, 10, and 20 mcg) on measures of cognition, mood, and subjective experience up until six hours after administration. Cognition and subjective experience were assessed using the Psychomotor Vigilance Task (PVT), Digit Symbol Substitution Test (DSST), Cognitive Control Task (CCT), Profile of Mood States, and 5-Dimensional Altered States of Consciousness rating scale.
Participants were healthy recreational psychedelic drug users (12 males; 12 females) aged 22.8 years on average. The majority was Caucasian; one participant was half Caucasian, half African American, one participant was Hispanic, and one participant was Indian. All had experience with at least one psychedelic substance, including DMT, ketamine, LSD, MDMA/ecstasy, psilocybin, and salvia. Participants also reported previous use of cannabis, amphetamines, cocaine, nicotine, and alcohol.
A training session took place before the test days to familiarize participants with the tests and procedures. Participants refrained from psychedelic substance use three months before the study, and other drug use at least one week before the study until completion of all four testing days. On the test days, smokers refrained from nicotine use two hours before the start and on the test days.
Participants spent the day in a quiet room with a window, equipped with a bed, a table, and chairs, where all assessments were conducted. Participants were screened for the presence of alcohol in breath, drugs of abuse in urine, and women were tested for pregnancy. When tests were negative, baseline subjective measures were taken using Visual Analogue Scales and Profile of Mood States to check whether participants still performed with 100% accuracy on the CCT.
At 10 a.m., drug administration took place. Thirty minutes to six hours post-administration, a test battery comprising questionnaires and computer tasks was conducted, and blood samples were taken. The test battery included additional measurements of creativity and empathy, pain perception, pharmacokinetics and pharmacodynamics, and neuroplasticity.
Study Results: Mood
The study revealed significant effects on all mood states. Tests indicated that the proportion of observations showing a decrease in anger and depression was significantly higher than the proportion of observations showing an increase in anger and depression. However, only half of the total observations showed a change from placebo and entered the binomial tests (tests with two possible outcomes).
Furthermore, the tests indicated that the proportion of observations showing an increase in anxiety, arousal, confusion, friendliness, and positive mood was higher than the proportion that showed a decrease on these mood scales. These tests included the majority of observations showing a change from placebo. There was no significant difference in the proportion of observations that showed an increased or decreased score from placebo on the other mood scales.
The positive effect on depression and anger is based on half of the total observations; only 48% of the observations showed a change from placebo after LSD administration.
Study Results: Cognition
Findings showed that speed of information processing was reduced. LSD increased self-rated drug-related states such as feeling under the influence, good drug effect, bad drug effect, feeling high, and drug liking, and decreased self-rated concentration and induced scores on most of the scales measuring changes in psychedelic-induced waking consciousness. Attention, cognitive control, mood, and self-rated levels of happiness, productivity, and time awareness were not affected, but analyses showed inter-individual variability in effects on mood, cognition and subjective drug states.
This study is the first to show individual variation to the effects of low doses of LSD (5 and 20 mcg) on cognition. Low doses of LSD can enhance attention in the majority of observations, which is in line with the anecdotal reports. However, LSD reduced the speed of information processing of the DSST, a task requiring a higher level of cognitive processes compared to the PVT.
Cognitive control was not affected by LSD, suggesting that a low dose might enhance cognitive performance that requires relatively limited cognitive processing, such as sustained attention. More studies are needed, including a broader range of cognitive functions to confirm these findings, which could stimulate research in patient populations suffering from attentional problems, including patients suffering from ADHD.
In contrast to anecdotal reports, the study shows a decrease in self-rated concentration. Although this finding seems to contrast the absence of LSD effects on self-reported concentration reported by Yanakieva et al., they administered lower LSD doses (a maximum of the 20 mcg tartrate corresponding to 16 mcg LSD base). It may indicate that the tipping point between absence and presence in experienced negative effects lies between these two doses. These findings demonstrate the interesting dissociation between objective task performance; the subjective experience showed that 63% of the observations rated performance deterioration.
The minimal LSD dose at which subjective and performance effects were notable is 5 mcg, and the most apparent effects were visible after 20 mcg.
Potential of Future Studies
Future studies in patient populations suffering from impaired attention are suggested to understand the inter-individual variation in response on cognitive and emotional processes. More studies, including more samples, would address this and could examine biological underpinnings of inter-individual variation in behavioural responses, and the potential biological markers associated with these individual differences.
Information on this study was taken from the journal article by Nadia R.P.W. Hutten, Natasha L.Mason, Patrick C.Dolder, Eef L.Theunissen, Friederike Holze, Matthias E.Liechti, Amanda Feilding, Johannes G.Ramaekers, and Kim P.C.Kuypers and published in ScienceDirect here.
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