Single-dose 1cp-LSD administration for canine anxiety: a pilot study

Anxiety affects an estimated 14–20% of domestic dogs and is commonly managed with medications such as selective serotonin reuptake inhibitors, benzodiazepines, tricyclics or alpha-2 agonists, often alongside behavioural support. According to the extracted text, these pharmacological options frequently have limited efficacy, require chronic use, and carry safety or dependency concerns, motivating the search for safer alternatives. In parallel, psychedelics have re-emerged in human psychiatric research for anxiety and depression, and preclinical work suggests that low or “micro” doses of classical psychedelics can produce anxiolytic and antidepressant effects in rodents without overt psychedelic phenomenology. Henríquez-Hernández and colleagues set out to explore whether a single microdose of 1-cyclopropionyl-d-lysergic acid diethylamide (1cP-LSD), a legal LSD analogue and putative prodrug of LSD, is safe in a dog and whether it produces measurable reductions in anxiety. Because no prior controlled studies in canines were reported, the aim was explicitly exploratory: to document behavioural responses and safety after one oral 5 µg dose (approximately 0.38 µg/kg for the subject) and to establish a preliminary foundation for future clinical trials and longer-term microdosing protocols in dogs with separation-related behavioural problems.

This pilot was a single-animal, open-label, observational trial conducted in the subject’s home. The participant was a 13-year-old spayed mixed-breed female dog (13 kg) with a lifelong history of separation-related anxiety. Ethical approval was obtained from the University of Las Palmas de Gran Canaria animal ethics committee and informed owner consent was secured. The trial took place on 10 January 2024 under continuous supervision by a veterinary ethologist and a veterinary toxicologist, with veterinary clinical support available if required. The intervention was a single oral administration of 5 µg 1cP-LSD (half of a 10 µg pellet), disguised in a piece of ham. The investigators note that 1cP-LSD is a lysergamide that hydrolyses to LSD in blood and that its exact pharmacokinetics relative to other analogues are uncertain. Behavioural assessment used a previously validated 17-item separation-anxiety questionnaire producing scores categorised from "no separation anxiety" to "severe separation anxiety"; the dog’s baseline score and subsequent behaviour were recorded. The owner also completed the Non-Romantic Attachment Scale to characterise owner attachment style. During the five-and-a-half-hour observation period the team implemented a pre-planned series of anxiety-provoking stimuli (for example, the owner leaving the house) at set intervals and qualitatively categorised responses as none, moderate, or intense. Observations were video-recorded and the owner was relied upon for primary reports of normality or change. Post-trial follow-up contact was maintained for 24 hours and for seven days thereafter. No blinding, randomisation, or inferential statistical analyses were reported; outcomes were described qualitatively and with selected quantitative scores (e.g. anxiety scale, attachment subscales).

Baseline assessment showed severe separation anxiety: the dog scored 29 on the 17-item anxiety questionnaire. The owner’s attachment-profile scores indicated a fearful-avoidant style with anxious features (reported subscale scores: fearful 9/12, anxious 8/12, avoidant 7/12; secure 4/8). Thirty minutes after ingesting 5 µg 1cP-LSD, the owner reported the dog’s behaviour as ‘‘completely normal’’; the dog interacted with the environment, wagged its tail and appeared docile. At about one hour the animal lay down to sunbathe; at 90 minutes an anxiety-provoking stimulus (owner leaving) initially produced barking and whining consistent with the dog’s typical response. According to the temporal observations, a shift in behaviour occurred from approximately two hours post-administration: the dog became calmer, did not follow the owner when they left, did not vocalise or exhibit typical effusive greeting behaviour on return, and drank water for the first time during the session. At three hours a repeated stimulus elicited minimal barking and the dog remained in place when returned to its spot. By about four hours the dog ate and continued to explore, climb stairs and interact; at five hours she was calm during the owners’ mealtime, a situation that had previously provoked anxiety. The trial concluded at 5.5 hours. No adverse effects were reported during observation or in the 24-hour follow-up: there were no episodes of agitation, aggression, loss of consciousness, vomiting, respiratory distress, or other clinically significant events. The investigators did not observe mydriasis (pupil dilation) or overt signs of a psychedelic experience (stumbling, howling, restlessness, fear). The authors note that the time course resembled human reports for comparable compounds, with a peak effect around 2–3 hours and a return toward baseline from about 5 hours. The analysis presented was descriptive; no inferential statistics or comparator data are reported. The investigators acknowledge that the continuous presence of two unfamiliar observers could have influenced behaviour and that a single-subject design limits generalisability.

Henríquez-Hernández and colleagues interpret this single-case observation as indicating that a single low oral dose of 1cP-LSD was well tolerated in this dog and temporally associated with a reduction in separation-related anxiety behaviours during the five-and-a-half-hour observation window. The authors emphasise that the anxiolytic-like effects appeared transient, with baseline behaviours returning from approximately 4–5 hours after intake, and they propose that a structured microdosing regimen over weeks to months would be required to evaluate cumulative therapeutic benefit, as in human trials. The discussion situates these findings within broader research on classical psychedelics: the investigators draw parallels to serotonergic mechanisms (noting 5-HT2A receptor involvement in humans) while acknowledging that the precise mechanism of action in dogs is unknown. They also consider non-pharmacological influences: the owner’s insecure, fearful-avoidant attachment profile may modulate the animal’s baseline anxiety and could have affected outcomes via bidirectional stress transmission; the presence of observers is also noted as a possible confound. The authors propose that future work should characterise individual animal stressors, behavioural markers (including body language), owner factors, tolerance, and longer-term dosing schedules. Key limitations acknowledged in the paper include the single-subject design, lack of controls or blinding, potential observer effects, and absence of pharmacokinetic data. The investigators recommend controlled clinical trials with larger samples and systematic microdosing protocols to determine safety, efficacy and mechanisms in canines. They also suggest that research in this area could inform questions about animal consciousness and cross-species comparisons of psychedelic effects, while reiterating that mechanistic and ethical issues require further study.

The authors state that, to their knowledge, this is the first reported pilot trial of 1cP-LSD administered with therapeutic intent in a dog. Under the conditions described, a single oral 5 µg dose was considered safe and was associated with a marked, temporally limited reduction in separation-related anxiety behaviours, with peak effects at about 2–3 hours and a gradual return to baseline from around 5 hours. These preliminary findings are presented as justification for conducting larger, controlled clinical studies to evaluate the potential utility of 1cP-LSD microdosing for dogs with separation-related behavioural problems.