Endocannabinoid System as Therapeutic Target of PTSD: A Systematic Review
Abstract
:1. Introduction
2. Materials and Methods
2.1. Literature Search
2.2. Study Selection
2.3. Quality Assessment
2.4. Data Extraction
2.5. Risk of Bias Assessment
3. Results
3.1. Search Results
3.2. Content Results
3.3. Quality and Risk of Bias Assessment
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Author | Year and Country | Period | Study Design | Study Sample | Treatment | Comparator Group | Measures | Outcome |
---|---|---|---|---|---|---|---|---|
Elms et al. [47] | 2019, US (Colorado) | 8 weeks | Retrospective study Grade: * | N = 11 (8 F, 3 M); mean age 39.91 ± 17.39; DSM-5 diagnosis of PTSD | N = 1: 9 mg/d (mean dose, range 1–16) CBD liquid oil spray; N = 4: 25 mg/d (mean dose, range 25–100) CBD capsule; N = 6: both formulations | None | Changes in PCL-5 score | Decline in PCL-5 mean scores of 21% (from 51.82 to 40.73) in 91% subjects at 4 weeks. Further decrease of 9% (to 37.14) in 75% subjects at 8 weeks. |
Rabinak et al. [52] | 2019, US (Michigan) | Acute study | Randomized, double-blind, placebo-controlled, between-subjects study Grade: **** | N = 71 (36 F, 35 M) age 20–45; N = 22: DSM-5 diagnosis of PTSD; N = 24: TEC; N = 25: HC | THC 7.5 mg capsule | Placebo | Threat-processing paradigm at fMRI (amygdala, mPFC/rACC activation and functional connectivity) | In the PTSD group THC lowered threat-related bilateral amygdala activity (drug x group interaction left: F(1,65): 5.131, p = 0.027; right: F(1,65) = 4.456, p = 0.039), increased mPFC activation (drug x group interaction F(2,65) = 4.887, p = 0.011), increased mPFC-right amygdala functional coupling (F(1,65) = 8.181, p = 0.006). |
Smith et al. [48] | 2017, Canada | 2 years, variable treatment duration and time to follow-up | Retrospective study Grade: *** | N = 100 veterans (3 F, 97 M); mean age 43; DSM-5 diagnosis of PTSD | Medical cannabis (THC and CBD at variable percentages), start dose 1 g/d, self-titrated based on clinical response, maximum dose 10 g/d | None | Changes in PTSD-related symptoms, pain, and social impact, scored 1–10 as reported in clinical charts | Decrease of PTSD aggregate symptoms score from 7 to 2.9 (59% reduction, ES 1.5, p < 0.0001), decrease of suicidal thoughts score from 4.1 to 0.9 (77% reduction, ES 1, p < 0.0001), decrease of pain score from 6.6 to 3.4 (48% reduction, ES 1.5), decrease of PTSD social impact score from 6.6 to 2.7 (59% reduction, ES 1.2, p < 0.0001) after treatment. |
Cameron et al. [40] | 2014, Canada | 43 months | Retrospective study Grade: ** | N = 104 males; mean age 32.7 (range 19–55); 91% of which affected by DSM-IV-TR PTSD | Nabilone, mean initial dose 1.4 mg/d (range 0.5–2), mean final dose 4 mg/d (range 0.5–6), mean length of treatment 11.2 weeks (range 1 day–36 weeks) | None | Changes in PCL-C scores | Significant reduction of PLC-C scores (54.7 ± 13 vs 38.8 ± 7.1, p = 0.001) after treatment, consistent with a reduction from moderate to mild-borderline symptoms. |
Greer et al. [49] | 2014, US (California) | 30 months | Retrospective study Grade: ** | N = 80 adults; DSM-IV diagnosis of PTSD | Medical cannabis (THC and CBD at variable percentages), start dose 1 g/d, self-titrated based on clinical response, maximum dose 10 g/d | None | Changes in CAPS scores | Decrease in total CAPS score (22.5 ± 16.9 vs 98.8 ± 17.6, p < 0.0001) in subjects using cannabis. Significant reductions in CAPS symptom cluster scores (Cannabis × Cluster: F(2,158) = 39.87, p < 0.0001). |
Jetly et al. [39] | 2014, Canada | Two periods of 7 weeks separated by a period of 2 weeks | Randomized, double-blind, placebo-controlled crossover study Grade: **** | N = 10 military male personnel; age 18–65; DSM-IV-TR diagnosis of PTSD, current distressing nightmares, and difficulty falling/staying asleep as evaluated by CAPS | Nabilone 0.5 mg (start dose) weekly titrated to a maximum of 3 mg | Placebo | Changes in CAPS Recurrent Distressing Dreams and Difficulty Falling or Staying Asleep items, CGI-C, PTSD Dream Rating Scale, WBQ scores, Sleep Diary | Significant reduction of CAPS Recurring and Distressing Dream Frequency (−1.9 ± 1.3 vs −0.4 ± 1.4, p = 0.05) and Intensity (−1.7 ± 1.3 vs −0.6 ± 1.1, p = 0.06) scores, significant lower CGI-C (1.9 ± 1.1 vs 3.2 ± 1.2, p = 0.05) score, significant increase of WBQ (49.3 ± 21.6 vs 23 ± 17.2, p = 0.04) score after treatment with nabilone. |
Roitman et al. [37] | 2014, Israel | 3 weeks | Non-randomized, open-label, adjusted doses, study Grade: *** | N = 10 (3 F, 7 M); mean age 52.3 ± 8.3; DSM-IV PTSD diagnosis | TCH oil 0.1 cc (=2.5 mg) bid, after 2 days raised to 0.2 cc (=5 mg) bid | None | Changes in CAPS, CGI, PSQI, NFQ, NES scores | Significant decrease in CAPS arousal (32.3 ± 4.73 vs 24.3 ± 9.11, p < 0.02), CGI-S (6 ± 0.47 vs 4.9 ± 0.99, p < 0.02), NFQ frequency of nightmares (0.81 ± 0.55 vs 0.44 ± 0.41, p < 0.04), NES (32.2 ± 11.29 vs 22.9 ± 8.7, p < 0.002), PSQI (17.20 ± 2.65 vs 13.9 ± 4.48, p < 0.05) scores after treatment with THC. |
Bonn-Miller et al. [50] | 2013, US (California) | Not specified | Cross-sectional study Grade: ** | N = 217 (26.7% F, 73.3% M); mean age 41.2 ± 14.9 (range 18–74 years); 40 (18.9%) affected by PTSD | Medical cannabis, flexible-dose (mean use: 3 times/d, 9–12 g/week) | None | Subjective help received from medical cannabis as measured by a 5-point-likert scale | Traumatic intrusions predicted cannabis helpfulness (beta 0.22, p < 0.01), as well as the use of cannabis for social anxiety problems (p < 0.004). |
Reznik [51] | 2012, Israel | 3 years | Naturalistic observational study Grade: ** | N = 167 25 pure PTSD, 43 PTSD + clinical depression, 88 PTSD + chronic pain | Medicinal cannabis (20–25% THC), range 2–3 g/d | None | Changes in CAPS, QOLS, CGI-I scores | Significant improvement in QOLS and pain scores in most cases, with some positive changes in CAPS scores. The majority of improved subjects belonged to comorbidity groups. |
Fraser [38] | 2009, Canada | 2 years of clinical observation; flexible duration of treatment with nabilone (depending on the clinical response) | Non-randomized, open-label study Grade: *** | N = 47 (27 F, 20 M); mean age 44 ± 9; DSM-IV-TR diagnosis of PTSD, treatment-resistant nightmares | Nabilone 0.5 mg (start dose) before bedtime, then titrated; doses were kept below 6 mg/d | None | Changes in the intensity of PTSD-related nightmares | 34 (72%) subjects experienced total cessation or significant reduction of nightmares. Nabilone discontinuation was successful in 4 (8%) subjects, whilst the others experienced a recurrence of nightmares. |
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Steardo, L., Jr.; Carbone, E.A.; Menculini, G.; Moretti, P.; Steardo, L.; Tortorella, A. Endocannabinoid System as Therapeutic Target of PTSD: A Systematic Review. Life 2021, 11, 214. https://doi.org/10.3390/life11030214
Steardo L Jr., Carbone EA, Menculini G, Moretti P, Steardo L, Tortorella A. Endocannabinoid System as Therapeutic Target of PTSD: A Systematic Review. Life. 2021; 11(3):214. https://doi.org/10.3390/life11030214
Chicago/Turabian StyleSteardo, Luca, Jr., Elvira Anna Carbone, Giulia Menculini, Patrizia Moretti, Luca Steardo, and Alfonso Tortorella. 2021. "Endocannabinoid System as Therapeutic Target of PTSD: A Systematic Review" Life 11, no. 3: 214. https://doi.org/10.3390/life11030214