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. 2022 Aug 26;36(10):1100–1117. doi: 10.1177/02698811221116926

Table 1.

All 34 included quantitative studies.

Study Design Disorder N (m/f) mean age Frequency and dosage AE measures Prior experience with the drug Acute AEs (number of participants*, % of participants*)
*When reporting is different, it is mentioned in the relevant row		 Late AEs (time of measurement) number of participants*, % of participants*)
*When reporting is different, it is mentioned
MDMA
PTSD
Mitchell et al. (2021) RCT III PTSD 90 (31/59), 41 years 3×: 80–120 mg + 50% (optional) CSSRS, Monitoring of AESIs: cardiac function, suicidal ideation, and substance abuse Lifetime MDMA use: 32% (MDMA group: 39%; Placebo group: 25%) SAEs
- Suicide attempts
- SI resulting in self-hospitalization
AESIs
- Suicidality (total)
- Cardiac events indicating QT prolongation		 MDMA (n = 46)
—
—
3, 7%
—		 Placebo (n = 44)
1, 2%
1, 2%
5, 11%
1, 2%		 TEAEs (18 weeks)
Muscle tightness
Decr Appetite
Nausea
Hyperhidrosis		 MDMA (n = 46)
29, 63%
24, 52%
14, 30%
9, 20%		 Placebo (n = 44)
5, 11%
5, 11%
5, 11%
1, 2%
Jardim et al. (2020) Open-label PTSD 3 (0/3), 40.3 years 3×: 75–125 mg + 50% (optional) SR NR Symptoms (freq of reported AEs, % of total sessions)
Somatic pains
Cough
Anguish		 MDMA (n = 3)
4, 44%
3, 33%
2, 22%		 Symptoms (7 days)
Somatic pains
Cough
Anguish		 MDMA (n = 3)
3, 4%
2, 3%
10, 14%
Monson et al. (2020), Wagner et al. (2019) Open-label PTSD 6 couples (6/6), 47 years 2×: 75–100 mg SR NR Symptoms
Anxiety
Upper resp tract infection
Fatigue
Nausea
Disturbed attention		 MDMA (n = 6)
5, 83%
2, 33%
1, 17%
1, 17%
1, 17%		 CSO (n = 6)
4, 67%
1, 17%
3, 50%
1, 17%
1, 17%		 Symptoms (7 days)
Fatigue
Anxiety
Headache		 MDMA (n = 6)
3, 50%
2, 33%
1, 17%		 CSO (n = 6)
—
1, 17%
—
Mithoefer et al. (2019), Mithoefer et al. (2011, 2013b, 2018), Oehen et al. (2013), Ot’alora (et al. 2018) RCT II with crossover PTSD 105 (44/61), 40.5 years 2–3×: 75–125 mg (vs 0–40 mg) +50% (optional) SR, TEAEs, CSSRS, PASAT, RBANS Lifetime MDMA use: 30% (MDMA group: 32%; control: 23%) Symptoms
Anxiety
Fatigue
Headache
Jaw clenching, tight jaw
Lack of appetite
Nausea		 MDMA (n = 72)
52, 72%
35, 49%
38, 53%
46, 64%
35, 49%
29, 40%		 Control (n = 31)
15, 48%
18, 58%
22, 71%
6, 19%
7, 23%
6, 19%		 Symptoms (7 days)
Anxiety
Fatigue
Insomnia
Low mood
Need > sleep
PTEAEs (1–2 months)
- Anxiety
- Depressed mood
- Irritability
- Anxiety attack		 MDMA (n = 72)
19, 26%
9, 13%
8, 11%
12, 17%
—
17, 24%
6, 8%
4, 6%
4, 6%		 Control (n = 31)
7, 23%
8, 26%
6, 19%
4, 13%
6, 19%
3, 10%
1, 3%
—
—
Bouso et al. (2008) RCT PTSD 4 (0/4), 36.7 years 1×: 50–75 mg UKU scale of secondary effects 0% Symptoms
Fatigue
Headache
Inner unrest		 MDMA (n = 2 reported on secondary effects)
2, 100%
2, 100%
2, 100%		 NR
Other disorders
Sessa et al. (2019, 2021) Open-label AUD 14 (8/6), 48 years 2×: 125 mg + 50% (optional) SR NR Abnormal rise in BP (n = 1)
No unexpected SAEs or AEs observed		 NR NR
Wolfson et al. (2020) RCT w/crossover EOLA 13 (3/10), 55.5 years 2×: 125 mg + 50% (optional) SR Lifetime ecstasy use: 56% (MDMA group: 54%; placebo group: 60%) Symptoms
Jaw clenching
Thirst
Dry mouth
Perspiration
Headache
No SAEs reported 		MDMA (n = 13)
11, 85%
11, 85%
9, 69%
9, 69%
8, 62%		 Placebo (n = 5)
1, 20%
2, 40%
1, 20%
—
1, 20%		 Symptoms (7 days)
Fatigue
Need > sleep
Insomnia
Anxiety
Jaw clenching
Low mood
TEAE (1 month)
Insomnia
Anxiety
Depression
Dissociation		 MDMA (n = 13)
12, 92%
9, 69%
8, 62%
8, 62%
8, 62%
6, 46%
2, 15%
1, 8%
1, 8%
1, 8%		 Placebo (n = 5)
3, 60%
2, 40%
2, 40%
2, 40%
1, 20%
3, 60%
1, 20%
—
—
—
Searchfield et al. (2020) RCT w/crossover Tinnitus 13 (9/4), 53.4 years 1×: 30 vs 70 mg NR NR NR NR
Danforth et al. (2018) RCT Social anxiety in adults with autism 12 (10/2), 32.8 years 2×: 75–125 mg SR 0% Symptoms
Anxiety
Diff. concentrating
Fatigue
Headache
Sensitivity to cold
No SAEs reported 		MDMA (n = 8)
6, 75%
5, 63%
4, 50%
4, 50%
4, 50%		 Placebo (n = 4)
1, 25%
1, 25%
1, 25%
1, 25%
—		 Symptoms (7 days)
Fatigue
Headache
Diff. concentrating
Low mood
Need more sleep
PTEAE (2 months)
Depressed mood
Suicidal ideation
Anxiety
Depression
Panic		 MDMA (n = 8)
5, 63%
5, 63%
4, 50%
4, 50%
3, 38%
2, 25%
2, 25%
1, 13%
1, 13%
1, 13%		 Placebo (n = 4)
2, 50%
1, 25%
—
2, 50%
2, 50%
—
1, 25%
—
1, 25%
—
Psilocybin
Depressive disorders
Carhart-Harris et al. (2021) RCT II MDD 59 (39/20), 39.1–43.3 years 2×: 25 mg Directed AE questions, daily monitoring 27% (Psilocybin group: 27%; control group: 28%) Symptoms
Headache
Nausea		 Psilocybin (n = 30)
13, 43%
4, 13%		 Escitalopram (n = 29)
5, 17%
—		 Symptoms (during 6-week trial period)
Headache
Nausea
Fatigue		 Psilocybin (n = 30)
20, 67%
8, 27%
2, 7%		 Escitalopram (n = 29)
15, 52%
9, 31%
7, 24%
Davis et al. (2020) RCT w/crossover MDD 24 (8/16), 39.8 years 2×: 20 and 30 mg/70 kg SR and CEQ 1.9% lifetime psychedelic use (immediate Tx: 1.7%; delayed Tx: 2.2%) Symptoms (% and mean severity from 1 to 5)
I felt like crying
Sadness
Feeling my heart beating
Emotional/physical suffering
Feeling my body shake
Pressure in chest/abdomen
I felt shaky inside
Despair
Anxiousness
Experience of fear
Isolation and loneliness
No related SAEs reported 		30 mg/70 kg (n = 24)
20, 83% (3.8)
17, 71% (3.5)
17, 71% (3.1)
16, 67% (3.9)
16, 67% (3.3)
16, 67% (3.8)
14, 58% (3.6)
14, 58% (3.4)
14, 58% (3.5)
14, 58% (2.9)
13, 54% (3.7)		 20 mg/70 kg (n = 24)
24, 100% (3.6)
21, 88% (4.0)
17, 71% (2.8)
21, 88% (3.7)
16, 67% (3.2)
16, 67% (3.3)
16, 67% (3.3)
14, 58% (3.4)
13, 54% (3.2)
12, 50% (3.3)
15, 63% (3.7)		 Symptoms (2 weeks)
Headache
Visual distortion
Tenseness		 30 mg/70 kg (n = 24)
7, 29%
2, 8%
2, 8%		 20 mg/70 kg (n = 24)
7, 29%
1, 4%
—
Carhart-Harris et al. (2016, 2018) Open-label TRD 20 (14/6), 44.1 years 2×: 10 and 25 mg SR, observed and post-treatment interview 35% Symptoms
Transient anxiety
Transient nausea
Transient paranoia
No related SAEs reported 		Psilocybin (n = 20)
15, 75%
5, 25%
3, 15%		 Symptoms (1 day)
Headache		 Psilocybin (n = 20)
8, 40%
End-of-life anxiety and depression
Griffiths et al. (2016) RCT w/crossover EOLA 51 (26/25, 56.3 years 1×: 1 vs 22 mg/70 kg SR and observed 45% (low-dose first: 56%, high-dose first: 36%)
Mean years since last use: 30.6 years		 Symptoms
Psychological discomfort
Anxiety
Physical discomfort
Nausea or vomiting
Systolic hypertension
No related SAEs reported 		22 mg/70 kg (n = 51)
16, 32%
13, 26%
11, 21%
8, 15%
17, 34%		 1 mg/70 kg (n = 51)
6, 12%
8, 15%
6, 12%
4, 8%
9, 17%		 Symptoms (1 day)
Headache		 Psilocybin (22 mg/70 kg) (n = 51)
18%
Ross et al. (2016) RCT w/crossover EOLA 29 (11/18, 56.3 years 1×: 0.3 mg/kg (vs 250 mg niacin) SR and observed 55% (psilocybin first = 50%; placebo first = 60%) Symptoms
Headaches/migraines
Transient anxiety
Nausea
Transient paranoid ideation
Transient thought disorder
No related SAEs reported 		Psilocybin (n = 29)
8, 28%
5, 17%
4, 14%
2, 7%
2, 7%		 NR
Grob et al. (2011) RCT EOLA 12 (1/11), 36–58 years 1×: 0.2 mg/kg NR 67% (between <1 year and >30 years ago) NR NR NR
Substance use disorders
Bogenschutz et al. (2015) Open-label AUD 10 (6/4), 40.1 years 1–2×: 0.3 and 0.4 mg/kg
2× (n = 7)
1× (n = 3)		 Adverse events case report and observed NR Symptoms
Nausea
Vomiting
Diarrhea		 Psilocybin (n = 10)
1, 10%
1, 10%
1, 10%		 Symptoms (36 weeks)
Headache
Insomnia		 Psilocybin (n = 10)
5, 50%
1, 10%
Johnson et al. (2014) Open-label Tobacco smoking 15 (10/5), 51 years 2–3×: 20 and 30 mg/70 kg Post-treatment SOCQ; next-day headache ratings 67%
Mean lifetime uses: 8 (1–17) Mean years since last use: 27 years (7–43)		 Symptoms (% and severity)
Anxiety
Feeling trapped
No SAEs reported 		Psilocybin (n = 15)
6, 40% (strong to extreme)
6, 40% (strong to extreme)		 Symptoms (1 day)
Headache		 Psilocybin (n = 10)
8, 80% (2.6, scale from 1 to 6)
Other disorders
Anderson et al. (2020) Open-label Demoralization in HIV+ gay men 18 (18/0), 59.2 years 1×: 0.3–0.36 mg/kg SR, observed, CEQ, AE interview Lifetime use of classic psychedelics: 5 (SD 3–23). Mean years since last use: 20 (1–32) Symptoms (% and severity)
Anxiety
Nausea
Headache
Paranoia
Severe hypertension
No related SAEs reported 		Psilocybin (n = 18)
8, 44% (severe)
6, 33% (severe)
5, 28% (moderate)
4, 22% (mild)
4, 22%		 Symptoms (3 months)
Headache
Fatigue
Insomnia
Anxiety
MA relapse
PTSD flashback		 Psilocybin (n = 18)
8, 44% (mild)
2, 11% (moderate)
2, 11% (moderate)
1, 6% (severe)
1, 6% (unexpected, moderate)
1, 6% (unexpected, moderate)
Schindler et al. (2020) RCT w/crossover Migraine 10 (3/7), 40.5 years 2×: 0.143 mg/kg Questions about AEs 20% Symptoms
Lightheadedness
Nausea
Anxiety
Tension/sore muscles		 Psilocybin (n = 10)
3, 30%
4, 40%
3, 30%
1, 10%		 Placebo (n = 10)
1, 10%
—
—
3, 30%		 Symptoms (1 day)
Headache attack
Migraine attack		 Psilocybin (n = 10)
2, 20%
5, 50%
Moreno et al. (2006) Dose-escalation OCD 9 (7/2), 40.9 years 1–3×: 0.1, 0.2 and 0.3 mg/kg NR 100% Hypertension in one patient
No AEs or related SAEs reported 		NR
Ayahuasca
Dos Santos et al. (2021) RCT SAD 17 (2/15), 24.9 years 1×: 2 ml/kg (0.68 mg/ml DMT) SR 0% Symptoms
Gastr. Discomfort/nausea
Vomiting
Drowsiness
Confusion
No SAEs reported 		Ayahuasca (n = 9)
4, 44%
3, 33%
2, 22%
2, 22%		 Placebo (n = 8)
—
—
—
—		 Symptoms (1 day)
Headache		 Ayahuasca (n = 9)
2, 22%
Palhano-Fontes et al. (2019) RCT TRD 14 (3/1)1, 39.7 years 1×: 1 ml/kg (0.36 mg/kg DMT) SR and observed 0% Symptoms
Nausea
Vomiting
Anxiety
Restlessness
Headache
No related SAEs reported 		Ayahuasca (n = 14)
10, 71%
8, 57%
7, 50%
7, 50%
6, 43%		 Placebo (n = 15)
4, 26%
—
11, 73%
3, 20%
8, 53%		 NR
Sanches et al. (2016), Osório et al. (2015) Open-label MDD 17 (3/14), 42.7 years 1×: 2.2 ml/kg (0.8 mg/ml DMT) SR 0% Symptoms
Vomiting
No related SAEs reported 		Ayahuasca (n = 17)
8, 47%		 NR
LSD
Schmid et al. (2020) Observational Various 18 (6/12), 49 years LSD: 100–200 μg (n = 11)
MDMA: 100–175 mg (n = 11)		 NR 39% NR NR
Müller et al. (2020) Case report Complex personality disorder 1 (0/1), 39 years 1×/week: 200 μg NR NR No AEs, related SAEs or physiological data SAEs reported NR
Gasser et al. (2014) RCT II EOLA 11 (7/4), 49.6 years 2×: 200 μg (vs 20 μg) SR (daily diary) and observed 8% Symptoms (frequency of sessions, % of total sessions and severity; 1 = mild, 2 = moderate, 3 = severe)
Illusion
Feeling cold
Feeling abnormal
Emotional distress
Anxiety
No related SAEs 		200 μg (n = 8)
16, 73% (1.8)
10, 45% (2.0)
9, 41% (2.3)
8, 36% (1.9)
5, 23% (2.2)		 20 μg (n = 3)
1, 17% (1.0)
—
2, 33% (1.0)
2, 33% (1.5)
3, 50% (2.3)		 Symptoms (1 day)
Feeling cold
Emotional distress
Illusion
Feeling abnormal		 200 μg (n = 8)
2, 9% (1.5)
2, 9% (1.0)
1, 5% (1.0)
1, 5% (1.0)		 20 μg (n = 3)
—
—
—
—

AESI: Adverse event of special interest; AUD: alcohol use disorder; BT: body temperature; CEQ: Challenging Experience Questionnaire; CSSRS: Columbia Suicide Severity Rating Scale; DBP: diastolic blood pressure; DMT: N,N-dimethyltryptamine; EOLA: end-of-life anxiety; HR: heart rate; LSD: lysergic acid diethylamide; MAP: mean arterial pressure; MDD: major depressive disorder; MDMA: 3,4-methyenedioxymethamphetamine; NR: not reported; OCD: obsessive compulsive disorder; PASAT: Paced Auditory Serial Addition Task; PTEAE: psychiatric treatment-emergent adverse event; PTSD: post-traumatic stress disorder; RBANS: Repeatable Battery for the Assessment of Neuropsychological Status; RCT: randomized controlled trial; RCT II: phase II randomized controlled trial; SAD: Social Anxiety Disorder; SAE: serious related adverse events; SBP: systolic blood pressure; SI: suicidal ideation; SR: spontaneously reported; TEAE: treatment-emergent adverse event; TRD: treatment-resistant depression; VAS: Visual Analog Scale.