Use of Medicinal Cannabis and Synthetic Cannabinoids in Post-Traumatic Stress Disorder (PTSD): A Systematic Review
Abstract
:1. Introduction
1.1. Post Traumatic Stress Disorder (PTSD)
1.2. Therapeutic Approaches for PTSD
1.3. Cannabis use in PTSD: A Coping Strategy?
1.4. Cannabis, Cannabinoids, and Their Role in PTSD
- (1)
- CB1 receptors are found in moderate to high levels throughout brain limbic structures, and have been shown to possess modulating properties on behaviors, including mood, stress, learning, and memory [4]: in fact, by activating the CB1 receptors in the amygdala, cannabis can potentially block the consolidation of aversive memories, fear, and anxiety; moreover, through stimulating CB1 receptors in the prefrontal cortex, cannabis may increase serotonin and, therefore, display antidepressant properties; finally, cannabis agonism on CB1 receptors in the hippocampus seems to improve neurogenesis, mood, and memory as well as causing decreases in hypervigilance, hyperarousal, and intrusive memories, effects which may contribute to the anxiolytic and antidepressant effects of cannabinoids [1,4,5,7]; conversely, animal studies have shown that a reduction in the number of CB1 receptors may be associated with heightened indices of anxiety and depression, especially if the disorder persists [4].
- (2)
- Stimulation of the limbic and paralimbic areas might decrease amygdala and hypothalamus activity, regulating the hypothalamic–pituitary axis and cortisol response, and, therefore, decreasing hypervigilance and hyperarousal [1,5]. Conversely, a low eCB tone contributes to amygdala hyperactivation as well as anxiety and hyperarousal symptoms characteristic of PTSD, including sleep disturbances, memory and cognitive impairments, depression, and suicidality [14]. Interestingly, a difference in gender has been evidenced, with males showing a higher degree of endocannabinoids released in response to a stressor and stronger physiological effects to cannabis compared to women [4,26,27];
- (3)
- (4)
- Cannabinoid modulation exerts effects on memory processes through alteration of the brain-derived neurotrophic factor (BDNF) concentrations in the hippocampus and the basolateral amygdala, as well as altering long-term potentiation in hippocampal neurons [27].
1.5. Therapeutic use of Synthetic Cannabinoids in PTSD
1.6. Aims of the Paper
2. Methods
2.1. Search Sources and Strategies
2.2. Study Selection
2.3. Data Extraction and Management
2.4. Characteristics of Included Studies
3. Results
3.1. Medical Cannabis
3.2. THC
3.3. CBD
3.4. Nabilone
4. Discussion
5. Conclusions
Author Contributions
Acknowledgments
Conflicts of Interest
References
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Study (Author(s), Year of Publication) | Sample Characteristics | Cannabinoid or Cannabis-Based Medicine Implicated | Control Group (If Any) | Dose (s) | ROA | Outcomes Measures Used | Main Findings |
---|---|---|---|---|---|---|---|
Bonn-Miller et al. (2014a) [14] | 170 patients at a medical cannabis dispensary in California | CBD + THC | Pts without PTSD | n.d. | n.d. | PCL-C CMMQ MSHQ AUDIT IDAS | Improvement of PTSD-related sleep disturbances but only 8/40 of PTSD subjects reported a reduction in PTSD symptoms. |
Earleywine and Bolles (2014) [17] | 650 combat-exposed male veterans | THC | None | unknown | Smoked, at least once per week | PCL-M CES | Significant expectations of cannabis-induced relief from PTSD symptomatology, particularly for intrusion, hyperarousal, then avoidance, and numbing. |
Elms et al. (2019) [25] | 11 PTSD outpatients | CBD | None | Flexible for 8 weeks | OS capsule or liquid spray once or twice per day based on severity of symptoms | PCL-5 | Decreased PTSD symptom severity at 8 weeks from baseline. |
Cameron et al. (2014) [28] | 104 male inmates with serious mental illness | Nabilone | None | Mean initial dose: 1.4 mg daily (0.5-2 mg) Mean final dose: 5 mg daily (0.5-6 mg) | n.d. | PCL-C GAF | Significant improvement in PTSD-associated insomnia, nightmares, PTSD symptoms. |
Fraser (2009) [33] | 47 patients with treatment-resistant PTSD | Nabilone | None | 0.5 mg titrated up to a max of 4 mg daily | OS 1 h prior to bedtime | Nightmare presence and intensity; hours of sleep | Reduction in nightmare intensity, subjective improvement in sleep time, quality of sleep, and reduction of daytime flashbacks and night sweats. |
Bonn-Miller et al. (2014b) [36] | 217 patients at a medical cannabis dispensary in California | CBD + THC | Pts without PTSD | n.d. | n.d. | n.d. | Reduction of stress, anxiety, depression, and PTSD symptomatology. |
Greer et al., (2014) [37] | 80 PTSD patients | CBD+THC | None | Unknown proportion | Smoked | CAPS | PTSD symptoms reduction. |
Wilkinson et al. (2015) [38] | 2276 PTSD veterans admitted to intensive PTSD treatment programs and divided into a) never cannabis users; b) cannabis users stoppers; c) continuing cannabis users; d) cannabis use starters | CBD+THC | Comparing groups | n.d. | n.d. | ASI MISS for PTSD | Starting cannabis use worsened PTSD symptoms. Stopping cannabis use improved PTSD symptoms. At follow-up, stoppers and never cannabis users had lower levels of PTSD symptoms, and starters had the highest levels of violent behavior. |
Tull et al. (2016) [39] | 202 subjects with and without PTSD with a co-occurring stimulant, cocaine or alcohol use disorder admitted to a SUD treatment facility | CBD + THC | Placebo | n.d. | n.d. | SCID-I CAPS MINI PANAS DUQ | Current PTSD was associated with greater subjective emotional reactivity to the trauma script only in subjects without cannabis use. Cannabis users (with and without PTSD) reported less subjective emotional reactivity than participants with PTSD but without cannabis use. |
Roitman et al. (2014) [40] | 10 PTSD outpatients from Israel | THC | None | 2x2.5 mg daily titrated to 5 mg x 2 daily | OS 1 h after waking up and 2 h prior to bed | PSQI NFQ NES | Reduction in nightmares and improvement in sleep quality. |
Johnson et al. (2016) [41] | 700 veterans enrolled in the primary care mental health integration program | THC | Placebo | n.d. | Smoked | TLFB ASSIST PCL-CPHQ-9 PQSIA BOMC | No association between cannabis use and less severe PTSD symptomatology. |
Jetly et al. (2015) [42] | 10 male military personnel with PTSD | Nabilone | Placebo | 0.5 mg titrated to 3 mg | OS 1 h prior to bed | CAPS sleep items PTSD dream rating scale Sleep diary CGI-C WBQ | Reduction in nightmares. |
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Orsolini, L.; Chiappini, S.; Volpe, U.; De Berardis, D.; Latini, R.; Papanti, G.D.; Corkery, J.M. Use of Medicinal Cannabis and Synthetic Cannabinoids in Post-Traumatic Stress Disorder (PTSD): A Systematic Review. Medicina 2019, 55, 525. https://doi.org/10.3390/medicina55090525
Orsolini L, Chiappini S, Volpe U, De Berardis D, Latini R, Papanti GD, Corkery JM. Use of Medicinal Cannabis and Synthetic Cannabinoids in Post-Traumatic Stress Disorder (PTSD): A Systematic Review. Medicina. 2019; 55(9):525. https://doi.org/10.3390/medicina55090525
Chicago/Turabian StyleOrsolini, Laura, Stefania Chiappini, Umberto Volpe, Domenico De Berardis, Roberto Latini, Gabriele Duccio Papanti, and John Martin Corkery. 2019. "Use of Medicinal Cannabis and Synthetic Cannabinoids in Post-Traumatic Stress Disorder (PTSD): A Systematic Review" Medicina 55, no. 9: 525. https://doi.org/10.3390/medicina55090525
APA StyleOrsolini, L., Chiappini, S., Volpe, U., De Berardis, D., Latini, R., Papanti, G. D., & Corkery, J. M. (2019). Use of Medicinal Cannabis and Synthetic Cannabinoids in Post-Traumatic Stress Disorder (PTSD): A Systematic Review. Medicina, 55(9), 525. https://doi.org/10.3390/medicina55090525