Article Figures & Data
Figures
- Figure 1
Psychedelic treatment room, Cleveland Clinic Lutheran Hospital.
Tables
Set and setting One’s mindset ("set") and the physical environment ("setting") can strongly influence psychedelic subjective effects. Appropriate preparation by the practitioner, which includes building a strong therapeutic alliance and administering the psychedelic in a supportive environment, will minimize adverse experiences and enhance therapeutic efficacy. Intention24 Defining and setting an intention for what one hopes to gain from a psychedelic experience may increase the likelihood of a powerful and therapeutic psychedelic experience. Ego dissolution Losing one’s sense of self is a key feature of the psychedelic experience that can produce positive effects, such as feelings of unity, or negative effects, such as anxiety. This experience tends to be limited to classic psychedelics (psilocybin, lysergic acid diethylamide) and does not usually occur with MDMA. Mystical experience This transformational state, sometimes elicited by psychedelics, is marked by ineffability, ego dissolution, positive mood, transcendence of time and space, and feelings of unity with ultimate reality. The degree to which participants have a mystical experience has been positively correlated with therapeutic effect with classic psychedelics, but not with MDMA. Challenging experience, bad trip A negative psychedelic experience is marked by fear, dysphoria, paranoia, or confusion. Preparation, setting an intention, and taking a psychedelic under the care of a therapist can reduce the risk. Many who have had a challenging psychedelic experience ultimately report it was helpful, though some report long-term psychological harms. Neuroplasticity In this adaptive process, neuronal connections (eg, dendritic spines, synaptic proteins) change in response to a stimulus or experience. This can lead to formation of new neuronal connections or extinction of previously established ones. Psychedelics may enhance neuroplasticity for weeks after exposure. Suggestibility25 The quality of readily and uncritically accepting and acting upon others’ suggestions is enhanced by psychedelics and may be helpful for psychotherapy. MDMA = 3,4-methylenedioxymethamphet amine
- TABLE 2
Potential acute effects and pharmacology of orally administered MDMA and psilocybin
MDMA30,31 Psilocybin18,19,48 Potential acute psychological effects Sense of well-being, relaxation, reduced anxiety, stimulation, euphoria, prosocial effects, heightened introspection, increased self-esteem, reduced fearfulness, increased empathy, altered sense of time, mystical experience Elevated mood, stimulation, enhanced introspection, illusions, visual perceptual changes, hallucinations (auditory, olfactory, tactile, gustatory, and visual), synesthesia, alterations in sense of time, enhanced feelings of connectedness, anxiety, fatigue, affective lability, mystical experience Potential acute physical effects28,29 Mydriasis; diaphoresis; increases in blood pressure, temperature, and heart rate; slight impairment in psychomotor performance; dry mouth; jaw clenching; bruxism Mydriasis, elevated or slowed heart rate, elevated or decreased blood pressure, nausea, increased or decreased tendon reflexes, tremor, dysmetria Most common adverse effects Anxiety, jaw clenching, muscle tightness, reduced appetite, nausea, dizziness, excessive sweating, restlessness, feeling jittery, blurred vision, pyrexia, irritability, panic attack Headache, nausea, visual perceptual effects, dizziness, fatigue, euphoric mood and mood alteration, anxiety, and paresthesia Time to peak effects 1–2 hours 1–2 hours Elimination half-life 8–9 hours 2–3 hours Duration of acute effects 4–6 hours 6 hours Primary neurotransmitters affected Serotonin, norepinephrine, dopamine Serotonin Metabolism Primarily hepatic, via cytochrome P450 (mainly CYP2D6) Rapidly undergoes hepatic first-pass metabolism and dephosphorylation into psilocin (psychoactive metabolite); psilocin then undergoes phase I and phase II (primary) metabolism in the small intestine and liver, with metabolites eventually excreted renally MDMA = 3,4-methylenedioxymethamphet amine
Psychiatric conditions
Bipolar disorder (personal or close family history)
Personality disorder (eg, antisocial, borderline, schizoid)
Psychotic disorder (personal or close family history)
Suicidal ideation (with intent or plan) or recent suicidal behaviorNonpsychiatric conditions
Arrhythmia (clinically significant)
Type 1 diabetes, type 2 diabetes (uncontrolled)
Hepatic dysfunction, depending on psychedelic metabolism
Uncontrolled hypertension
Myocardial infarction (lifetime history)
Pregnancy or breastfeeding
QTc prolongation
Seizure disorder
Stroke (lifetime history)
Tachycardia
Unstable thyroid disease
