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Harm Reduction Education 
for Veterinary Professionals

What to tell PPs

What to do with an intoxication

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As humans begin to explore psychedelic medicine applications, we anticipate that our animals will have increased risk of exposure.  Our lack of information does not prevent the exposure of our patients to these substances.  As a community of veterinary practitioners, we need to remain informed about the risks as well as potential benefits to our patients. 

 

Our clients and our patients are looking to us for answers as the field of psychedelic medicine unfolds - we better get to work!

Here's what we know so far....

Cannabis

General Information

  • Ongoing clinical trials in humans are utilizing fixed dose equivalent to between 1-4mg/kg(1)

  • In humans

    • Onset of MDMA effects occurs 30-60 minutes after oral administration

    • Peak effects appear 75-120 minutes post drug administration

    • Duration of effects lasts from 3-6 hours with most effects returning to baseline or near-baseline levels 6 hours after drug administration

    • Elimination half-life of active doses of MDMA is 8-9 hours

Dosing & Toxicity Information

  • Ongoing clinical trials in humans are utilizing fixed dose equivalent to between 1-4mg/kg(1)

  • In humans

    • Onset of MDMA effects occurs 30-60 minutes after oral administration

    • Peak effects appear 75-120 minutes post drug administration

    • Duration of effects lasts from 3-6 hours with most effects returning to baseline or near-baseline levels 6 hours after drug administration

    • Elimination half-life of active doses of MDMA is 8-9 hours

Species-specific information

  • Ongoing clinical trials in humans are utilizing fixed dose equivalent to between 1-4mg/kg(1)

  • In humans

    • Onset of MDMA effects occurs 30-60 minutes after oral administration

    • Peak effects appear 75-120 minutes post drug administration

    • Duration of effects lasts from 3-6 hours with most effects returning to baseline or near-baseline levels 6 hours after drug administration

    • Elimination half-life of active doses of MDMA is 8-9 hours

MDMA

General Information

  • Ongoing clinical trials in humans are utilizing fixed dose equivalent to between 1-4mg/kg(1)

  • In humans

    • Onset of MDMA effects occurs 30-60 minutes after oral administration

    • Peak effects appear 75-120 minutes post drug administration

    • Duration of effects lasts from 3-6 hours with most effects returning to baseline or near-baseline levels 6 hours after drug administration

    • Elimination half-life of active doses of MDMA is 8-9 hours

Dosing & Toxicity Information

Species-specific

Psilocybin

Data from MAPS studies and other researchers’ published literature show that MDMA produces sympathomimetic effects that include transient, self-limiting increases in heart rate (HR) and blood pressure that were well-tolerated by healthy individuals [11, 13-15, 30, 32, 37-41] and study participants. Most people did not experience elevations that exceeded those seen after moderate exercise. Risks posed by elevated blood pressure were addressed by excluding candidates with a history of cardiovascular, cerebrovascular disease, or with pre-existing uncontrolled hypertension, and by regularly monitoring blood pressure and pulse throughout Experimental Sessions. Common reactions from MDMA reported in the literature and clinical trials were transient and diminished as drug effects waned during the session and over the next one to 7 days

The most MAPS MDMA Investigator’s Brochure U.S. 13th Ed: 22 March 2021 Page 13 of 227 commonly reported adverse events (AEs) in a pooled analysis of six Phase 2 studies were psychiatric symptoms, most commonly anxiety, depressed mood, irritability, and panic attacks. Participants reported experiencing anxiety, dizziness, fatigue, headache, jaw clenching/tight jaw, lack of appetite, and nausea during MDMA-assisted dosing sessions [33]. Most AEs were mild to moderate and lasted no longer than 7 days.

MDMA concomitantly promotes release, inhibits reuptake, and extends duration of serotonin, norepinephrine, and dopamine in the synaptic cleft to increase serotonergic, noradrenergic, and dopaminergic neurotransmission. MDMA is a triple monoamine reuptake inhibitor, and similar drugs in this class have been found to exert potent anti-depressant activity with a favorable safety profile in clinical trials [19, 20]. MDMA produces anxiolytic and prosocial effects through release of the monoaminergic neurotransmitters, with the greatest effect on serotonin, followed by norepinephrine and dopamine [21-25]. Subjective effects of MDMA can include increased compassion for self and others, reduced defenses and fear of emotional injury, and making unpleasant memories less disturbing while enhancing communication and capacity for introspection [26-29]. These factors taken together provide the opportunity for a corrective emotional experience in the context of therapy. Many of the therapeutic effects of MDMAassisted therapy are evident within a short period of treatment, often after the initial session. Increased feelings of interpersonal closeness, changes in social perception, and reduced anxiety might make MDMA a suitable pharmacological adjunct to enhance therapy for treatment of anxiety disorders, such as PTSD, social anxiety, and anxiety associated with other conditions.

MDMA may reduce responsiveness to changes in water/salt balance after normal and increased water consumption [42]. MDMA is also a mild immunosuppressant [43]. However, the clinical relevance of this observation is not clear as a review of infections, particularly upper respiratory tract infections (URTI) in the time of the COVID-19 pandemic did not reveal an increase in the MDMA groups compared to placebo (see Section 6.4.1.3 Adverse Events Summary).

MDMA was found to robustly MAPS MDMA Investigator’s Brochure U.S. 13th Ed: 22 March 2021 Page 14 of 227 influence human emotional status in a unique way [47] without adversely affecting physiological functions or perception, such as visual perception or cognition [12, 14, 16, 17].

MDMA possesses a complex pharmacological profile that is dominated by its effects as a monoamine releaser and reuptake inhibitor, with additional effects on limiting neurotransmitter production and degradation. Its prominent effects on serotonin differentiate it from amphetamine and methamphetamine, which primarily act on norepinephrine and dopamine pathways [21, 48]. In the Merck Index, MDMA resides in the Entactogen class [49]. Entactogens contain a ringsubstituted amphetamine core, belong to the phenethylamine class of psychoactive drugs, and are described as promoting acceptance and compassion for self and others, changing recognition and response to emotions, and increased interpersonal closeness [27, 50-52]. In comparison to anxiolytics, antidepressants and atypical antipsychotics, steady state levels in blood are not required for MDMA to function as a catalyst to therapy.

Additional MDMA research studies supported by the sponsor include a randomized, placebocontrolled, double-blind study of the effects of 100 mg MDMA on startle response, a study of MDMA pharmacokinetics in healthy volunteers and people with impaired liver function, and a study of the effects of fasting on MDMA pharmacokinetics (see Table 5).

Phase 2 investigations of MDMA-assisted therapy for treatment of PTSD (see Table 4: Summary of Completed Sponsor Supported Studies with MDMA). The pooled Phase 2 efficacy results in PTSD participants indicate that MDMA-assisted therapy administered in a controlled clinical setting demonstrated that the treatment was safe and efficacious among patients with moderate to severe PTSD

d. Research into the pharmacological, physiological, or psychological effects of MDMA began in the 1950s, when the U.S. Army administered MDMA to guinea pigs, monkeys, mice, rats, and dogs as part of a military research programMDMA possesses a complex pharmacological profile that is dominated by its effects as a monoamine releaser and reuptake inhibitor. Its prominent serotonergic effects differentiate it from amphetamine and methamphetamine, which primarily act on dopamine and norepinephrine [21, 48]. MDMA also has a complex profile from a pharmacokinetics perspective and has been demonstrated in multiple animal models to follow nonlinear pharmacokinetics, with increased doses resulting in disproportionate increase in exposure to the parent compound (see Section 4.2 Pharmacodynamic and Product Metabolism in Animals). Additionally, MDMA exhibits pharmacodynamic drug interactions with other drugs commonly used in psychiatry. In the following sections, the pharmacology of MDMA is presented based on nonclinical animal studies from both primary literature and sponsor conducted studies.

n the 1960s through the early 1970s, researchers began to investigate the compounds in psilocybin on dogs specifically.2,3 However, this wpopular use of the psilocybin mushroom includes its potential to enhance the hunting ability of working dogs, which has some scientific support from a study published in 2015 by Bennett et al.4

  1. Higgins GA, Carroll NK, et al. Low doses of psilocybin and ketamine enhance motivation and attention in poor performing rats: Evidence for an antidepressant property. Frontiers in Pharmacology. 2021;12:299. https://www.frontiersin.org/article/10.3389/fphar.2021.640241

  2. Fischer R, Hill RM, Warshay D. Effects of the psychodysleptic drug psilocybin on visual perception. Changes in brightness preference. Experientia. 1969;25:166–169. https://doi.org/10.1007/BF01899102

  3. Pickworth WB, Sharpe LG, Martin WR. Transcallosally evoked potentials and the EEG in the decerebrate dog: Actions of tryptaminergic, dopaminergic and adrenergic agonists, Electroencephalography and Clinical Neurophysiology,1977;42:809-816. https://doi.org/10.1016/0013-4694(77)90234-6

  4. Bennett BC, Alarcón R. Hunting and hallucinogens: The use psychoactive and other plants to improve the hunting ability of dogs. J Ethnopharmacol. 2015;171:171-183. doi:10.1016/j.jep.2015.05.035

  5. Torsten P, Seifert J, et al. The pharmacology of psilocybin. Addiction Biology. 2002;7:357-364. doi.org/10.1080/1355621021000005937

  6. Weidmann, H, Taeschler M, Konzett H. Zur Pharmakologie von Psilocybin, einem Wirkstoff aus. Psilocybe mexicana Heim. Experientia.1958;14:378–379. https://doi.org/10.1007/BF02159166

  7. Maxwell GM, Kneebone GM, Elliott RB. The effect of psilocybin upon the systemic, pulmonary, and coronary circulation of the intact dog. Arch Int Pharmacodyn Ther. 1962 May 1;137:108-15. PMID: 14471633.

  8. Brown J, Miller DM, et al. Hexokinase Isoenzyme in Liver and Adipose Tissue of Man and Dog. Science. 1967;155-3759:205-207. doi:10.1126/science.155.3759.205

Dog 28-Day General Toxicology ↓ weight gain 9, 15 mg/kg ↓ testicle size ↑ prostate size Deaths at 15 mg/kg

. Studies of MDMA have been conducted in primates and rodents. Primate species studied include baboon, macaque, rhesus monkey, and squirrel monkey, and rodents include mice and rats. Studies of circadian rhythm have occurred in hamsters [89]. Beginning in the mid-2000s onwards, reports re-examining these effects have questioned the applicability of allometric interspecies scaling models for MDMA [73, 90, 91].

 
 
 
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Psychoactive Substance Exposure in Animals
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