This placebo-controlled animal study (n=40) investigated the effects of ketamine (0.5-3 mg/kg) and psilocin (0.05-0.075 mg/kg) microdosing (x3) on anxiety-related explorative behaviour in rats and found that both substances caused mild anxiety as measured by a reduction of explorative behaviour on an elevated open surface.
Abstract of Psilocin and ketamine microdosing in rats
“Introduction: Short-term moderate doses of serotonergic and dissociative hallucinogens can be useful in the treatment of anxiety. Recently, a trend has developed for long-term intermittent ‘microdosing’ (usually one-tenth of a ‘full’ active dose), with reports of long-lasting relief from anxiety and related disorders; however, there is no scientific evidence for the efficacy of therapeutic microdosing nor to show its lasting effects. The objective of this study was to test for lasting effects on anxiety in rats after microdosing with ketamine or psilocin.
Methods: Over 6 days, Wistar rats (N=40) were administered ketamine (0.5 or 3 mg/kg), psilocin (0.05 or 0.075 mg/kg), or saline on three occasions. A 5-min elevated plus-maze test was conducted 48 h after the final drug treatment (N=8). Dependent variables were entries (frequency), spent time (%), and distance traveled (cm) in each zone, as well as total frequency of rears, stretch-attend postures, and head dips. Statistical analyses of drug effects used separate independent one-way analysis of variance and pair-wise comparisons using independent t-tests.
Results: Statistical effects were modest or borderline and were most consistent with a mildly anxiogenic profile, which was significant at lower doses; however, this conclusion remains tentative. The lower doses of ketamine and psilocin produced comparable effects (to one another) across each variable, as did the higher doses.
Discussion: This pattern of effects may suggest a common (e.g. neurotransmitter/receptor) mechanism. We conclude that microdosing with hallucinogens for therapeutic purposes might be counter-productive; however, more research is needed to confirm our findings and to establish their translational relevance to clinical ‘psychedelic’ therapy.“
Authors: Rachel R. Horsley, Tomáš Páleníček, Jan Kolin & Karel Valeš
Summary of Psilocin and ketamine microdosing in rats
Ketamine is a dissociative anesthetic with psychedelic effects at subanaesthetic doses, and has also substantial affinity for the serotonin transporter, as well as additional effects on dopamine and opioid neurotransmission. Psilocin and psilocybin act as competitive agonists at 5-HT receptors.
Although psychedelic hallucinogens and dissociative anaesthetics have distinct pharmacological properties, they exert some of their psychomimetic effects through a common pathway. This is why research has oriented to psychedelic hallucinogens and dissociative anaesthetics as deleterious to mental health.
Contemporary research suggests that psilocybin and ketamine can have therapeutic properties when administered at moderate psychomimetic doses. Two daily doses of intranasal ketamine (50 mg) produced minimal subjective psychedelic effects. Recent trends have developed for self-administering ‘microdoses’ of psychedelic drugs, such as psilocybin, lysergic acid, ketamine, and methoxetamine, on an intermittent regime, which is intended to be ‘sub-perceptual’, and to treat psychological ill-health, as well as enhancing creativity, spirituality, and social relationships.
Currently, there is no published scientific research on therapeutic microdosing with serotonergic or dissociative psychedelics. A preclinical model would allow for microdosing drug testing and development, as well as understanding the neural mechanisms that may be involved.
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http://dx.doi.org/10.1097/FBP.0000000000000394
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Cite this paper (APA)
Horsley, R. R., Páleníček, T., Kolin, J., & Valeš, K. (2018). Psilocin and ketamine microdosing: effects of subchronic intermittent microdoses in the elevated plus-maze in male Wistar rats. Behavioural pharmacology, 29(6), 530-536.
Study details
Compounds studied
Ketamine
Psilocybin
Topics studied
Anxiety
Microdosing
Study characteristics
Animal Study
Participants
40
Rodents
Authors
Authors associated with this publication with profiles on Blossom
Tomáš PáleníčekTomas Palinek is a researcher and psychiatrist in the Czech Republic where he studies a variety of psychedelics at the NIHM.