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Table 2 Endocannabinoid system

From: The relationship between cannabis and anorexia nervosa: a scoping review

Authors (year)

Study design

Participants

Methods, Interventions, and observations

Outcomes of Interest

Ishiguro et al., 2011 [17]

Case–control

235 AN, 1244 HC (all female)

Observed single-nucleotide polymorphisms related to circulating endocannabinoids from blood samples

• Val195 allele of GPR55 was more frequent in AN compared to HC (odds ratio = 1.30, 95% Cl: 1.02–1.66, p < 0.04)

Ando et al., 2014 [18]

Case–control

376 RAN, 387 BPAN, and 605 HC (all female)

Extracted genomic deoxyribonucleic acid related to circulating endocannabinoids from blood samples

• 385A allele was less frequent in AN compared to HC (odds ratio = 0.799, 95% CI 0.653–0.976, p = 0.028)

• 385A allele was less frequent in RAN compared to BPAN (odds ratio = 0.717, 95% CI: 0.557–0.922, p = 0.0094)

González et al., 2021 [19]

Case–control

221 AN, 396 HC (all female)

Screened single-nucleotide polymorphisms in CB1 & 2 from blood samples. Measured Symptom Checklist 90 Revised, Eating Disorders Inventory Test-2, and qualitative questionnaires

• genotype rs806369-TT and haplotype​ rs806368/rs1049353/rs806369 of CB1 were associated with lower weight in AN (40.55 ± 1.61 kg, vs. 45.47 ± 0.49 kg, mean difference = -4.92 kg, 95% CI: –7.74, – 1.46, p = 0.004) and BMI (16.09 ± 0.44 kg/m2, vs. 17.47 ± 0.15 kg/m2, mean difference = -1.38 kg/m2, 95% CI: -2.23, -0.33, p = 0.008)

• rs806374 of CB1 were associated with ED behaviors in AN (98.89 ± 4.90 vs. 83.93 ± 4.18, mean difference = – 14.96, 95% CI: – 26.820, – 1.710, p = 0.027)

• rs3003335 and rs6658703 of CB2 were associated with ED behaviors in AN (87.13 ± 3.66 vs. 104.69 ± 6.61, mean difference = 17.56, 95% CI: 2.153, 32.220, p = 0.026)

Gérard et al., 2011 [20]

Cross-sectional

14 AN, 19 HC (all female)

Performed positron emission tomography imaging to assess CB1 availability. Measured Eating Disorders Inventory Test and Eating Disorder Evaluation Scale

• CB1 availability was significantly higher in AN compared to HC (+ 24.5%, p = 0.0003; see Gérard et al. Figure 2B for supporting statistical values)

• Positive association between CB1 availability and drive for thinness in AN (correlation coefficient = 0.86, p = 0.001)

Tam et al., 2021 [21]

Combined cross-sectional longitudinal

67 in UWAN state, 27 in WRAN state, 84 HC (all female)

Measured levels of endocannabinoids through hair samples in all participants during the cross-sectional period (T1). Levels of endocannabinoids were measured again in the longitudinal period (T2) in participants in UWAN who experienced ≥ 12% increase in BMI

AEA:

• Elevated in UWAN (p = 0.021) and WRAN (p = 0.006) compared to HC in T1

• Decreased in UWAN during T2 compared to T1 (p = 0.022)

2-AG:

• NS differences in T1 or T2 between groups

OEA:

• Elevated in UWAN compared to HC in T1 (p = 0.003)

• Decreased in UWAN during T2 compared to T1 (p = 0.018)

PEA;

• Elevated in UWAN compared to HC in T1 (p = 0.018)

• Decreased in UWAN during T2 compared with T1 (p = . 028)

SEA:

• Elevated in UWAN compared to WRAN in T1 (p = 0.018)

• Elevated in UWAN compared to HC in T1 (p < 0.001)

• Decreased in UWAN during T2 compared with T1 (p = 0.018)

*See Tam et al. Figure 2 for supporting statistical values

Monteleone et al., 2015 [22]

Pre-meal/Post-meal study

7 in UWAN state [1 women, 6 man], 7 in WRAN state [2 women, 5 men], 7 HC [2 women, 5 men]

Measured levels of endocannabinoids through plasma after a 13-h fasting period, and 15 min and 120 min after eating for both hedonic and non-hedonic foods

AEA:

• Progressively decreased after eating both foods (F [3, 18] = 17.99, p < ​​0.00001) consistent in all groups

2-AG:

• NS differences in UWAN

• Progressively increased after eating both hedonic and non-hedonic foods in WRAN (See Monteleone et al. Figure 2 for supporting statistical values)

• Progressively decreased after eating hedonic foods compared to non-hedonic foods in HC (See Monteleone et al. Figure 2 for supporting statistical values)

OEA:

• Lower after eating hedonic foods compared to non-hedonic foods (F [1, 18] = 6.30, p = 0.02) consistent in all groups

PEA:

• Progressively decreased after eating hedonic and non-hedonic foods (see Monteleone et al. Figure 5 for supporting statistical values) consistent in all groups

Piccolo et al., 2019 [23]

Pre-meal/Post-meal study

15 in UWAN state, 10 in WRAN state, 9 HC

*Gender/sex not reported

Measured levels of endocannabinoids through plasma after an 8-h fasting period, and 120 and 240 min after eating

AEA:

• Lower in AN compared to HC at all time points (5.83 ± 0.44 pmol/ml vs. 2.85 ± 0.34 pmol/ml, p < 0.001)

• Elevated in UWAN & WRAN during fasting (4.69 ± 0.73 pmol/ml vs. 2.85 ± 0.34 pmol/ml and 4.64 ± 0.51 pmol/ml vs. 2.81 ± 0.22 pmol/ml, p < 0.001)

• Elevated in UWAN & WRAN after 240 min (1.70 ± 0.26 pmol/ml vs. 2.85 ± 0.34 pmol/ml and 1.48 ± 0.30 pmol/ml vs. 2.81 ± 0.22 pmol/ml, p < 0.05)

2-AG:

• NS differences between participants or time points

Baenas et al., 2023 [24]

Cross-sectional

27 AN, 29 HC (all women)

Measured levels of endocannabinoids through plasma after a 12-h fasting period

AEA:

• NS differences in AN compared to HC

• Lower levels were associated with higher BMI and higher emotional dysregulation in AN

2-AG:

• NS differences in AN compared to HC

• Higher levels were associated with worsened psychopathological states in AN

  1. *CI = Confidence intervals; p < 0.005 = Significant; NS = Not Significant; RAN = Restrictive type AN; BPAN = Binge/purge type AN; UWAN = Underweight AN; WRAN = Weight restored AN; T1 = Cross-sectional period; T2 = Longitudinal period; BMI = Body mass index