The Use of a Synthetic Cannabinoid in the Management of Treatment‐Resistant Nightmares in Posttraumatic Stress Disorder (PTSD)
Open accessAbstract
UNLABELLED: This is the report of an open label clinical trial to evaluate the effects of nabilone, an endocannabinoid receptor agonist, on treatment-resistant nightmares in patients diagnosed with posttraumatic stress disorder (PTSD). METHODS: Charts of 47 patients diagnosed with PTSD and having continuing nightmares in spite of conventional antidepressants and hypnotics were reviewed after adjunctive treatment with nabilone was initiated. These patients had been referred to a psychiatric specialist outpatient clinic between 2004 and 2006. The majority of patients (72%) receiving nabilone experienced either cessation of nightmares or a significant reduction in nightmare intensity. Subjective improvement in sleep time, the quality of sleep, and the reduction of daytime flashbacks and nightsweats were also noted by some patients. The results of this study indicate the potential benefits of nabilone, a synthetic cannabinoid, in patients with PTSD experiencing poor control of nightmares with standard pharmacotherapy. This is the first report of the use of nabilone (Cesamet; Valeant Canada, Ltd., Montreal, Canada) for the management of treatment-resistant nightmares in PTSD.
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- Findingown data
Of the 47 patients, 6 had a satisfactory reduction in nightmare severity on nabilone.
“Thirty-four (72%) patients experienced total cessation or lessening of severity of nightmares (28 patients had total cessation of nightmares and 6 had satisfactory reduction).”
Quote in the paperNot a substantial claim - Findingown data
Among 47 PTSD patients with treatment-resistant nightmares, 34 (72%) experienced total cessation or lessening of severity of nightmares after adjunctive nabilone was added to their existing medications.
“The majority of patients (72%) receiving nabilone experienced either cessation of nightmares or a significant reduction in nightmare intensity.”
- Also stated in: § Results · plain
“Thirty-four (72%) patients experienced total cessation or lessening of severity of nightmares (28 patients had total cessation of nightmares and 6 had satisfactory reduction).”
Quote in the paperSubstantial claim - Also stated in: § Results · plain
- Findingnone given
No tolerance to nabilone was observed among the patients.
“No tolerance to nabilone was observed among the patients.”
Quote in the paperSubstantial claim - Findingown data
Thirteen (28%) of the 47 patients experienced mild-to-moderate side effects shortly after nabilone initiation, leading to discontinuation of nabilone therapy.
“Thirteen (28%) patients experienced mild-to-moderate side effects (shortly following nabilone initiation), leading to discontinuation of nabilone therapy.”
Quote in the paperNot a substantial claim - Findingown data
Discontinuation of nabilone was successful in four patients following 4-12 months of therapy, with nightmares not returning or returning at a reduced level not needing further medication control.
“The discontinuation of medication was successful in four patients following 4-12 months of nabilone therapy (nightmares did not return or returned at a reduced level, not needing further medication control)”
Quote in the paperNot a substantial claim
- Findingown data
Patients other than the four successfully discontinued experienced a recurrence of nightmares upon nabilone withdrawal, usually within the first two nights.
“whereas the other patients experienced a recurrence of nightmares upon nabilone withdrawal (usually within the first two nights).”
Quote in the paperSubstantial claim - Findingown data
Of the 47 patients, 28 had total cessation of nightmares on nabilone.
“Thirty-four (72%) patients experienced total cessation or lessening of severity of nightmares (28 patients had total cessation of nightmares and 6 had satisfactory reduction).”
Quote in the paperSubstantial claim - Study design and conductcitation
Diagnoses for the study were confirmed by DSM-IV-TR criteria using the Posttraumatic Stress Diagnostic Scale.
“Diagnoses for the study were confirmed by DSM-IV-TR criteria using a recognized PTSD questionnaire, the Posttraumatic Stress Diagnostic Scale [9].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [9] 9. Foa EB, Cashman L, Jaycox L, Perry K. The validation of a self-report measure of posttraumatic stress disorders. Psychol Assess 1997;9:445-451. source
- Study design and conductown data
All patients had at least a 2-year history of PTSD-related nightmares that had not responded to conventional therapies.
“All patients had at least a 2-year history of PTSD-related nightmares that had not responded to conventional therapies (Tables 1 and 2).”
Quote in the paperSubstantial claim - Interpretationown data
Nabilone has beneficial effects beyond its official indication in abolishing or greatly reducing nightmares that persisted despite treatment with conventional PTSD medications.
“A chart review of patients diagnosed with PTSD who were referred to a private psychiatric clinic suggests that the synthetic cannabinoid, nabilone, has beneficial effects beyond its official indication in regard to abolishing or greatly reducing nightmares that persisted in spite of treatment with conventional PTSD medications.”
- Also stated in: § Conclusion · hedged
“Nonetheless, on the basis of these retrospective findings, nabilone appears to be a significant treatment for nightmares in the PTSD population.”
- Also stated in: § Abstract · hedged
“The results of this study indicate the potential benefits of nabilone, a synthetic cannabinoid, in patients with PTSD experiencing poor control of nightmares with standard pharmacotherapy.”
Quote in the paperSubstantial claim - Also stated in: § Conclusion · hedged
- Premisecitation
A single published case study reported that nabilone reduced nightmares when it was used to replace a patient's smoked marijuana for relief of PTSD symptoms.
“On the basis of observations published in a single case study that mentioned nabilone's reduction of nightmares when it was employed to replace a patient's use of smoked marijuana for the relief of PTSD symptoms [22]”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [22] 22. Berlach DM, Shir Y, Ware MA. Experience with the synthetic cannabinoid in chronic noncancer pain. Pain Med 2006;7:25-29. source
- Interpretationreasoning
The absence of observed tolerance to nabilone may indicate its potential longer-term safety and efficacy.
“This may indicate its potential longer-term safety and efficacy.”
Quote in the paperSubstantial claim
- May combine two claims. 7
- The quote only partly states this claim. 1
- Classified as probably not a substantial claim. 13
May combine two claims. The quote only partly states this claim.
Findingown dataSome patients subjectively reported improvement in sleep time, quality of sleep, reduction of daytime flashbacks, and cessation of nightsweats while on nabilone.
“In some cases, the benefits including an improvement in sleep time and a reduction of daytime flashbacks were subjectively noted.”
- Also stated in: § Results · plain
“Several patients also stated that they no longer experienced nightsweats while on nabilone.”
Quote in the paperSubstantial claim- Also stated in: § Results · plain
May combine two claims.
Findingown dataOnce effective relief of nightmares was achieved, no further increase in nabilone dose was necessary and patients' doses remained stable.
“Once effective relief of nightmares was achieved, no further increase in nabilone was necessary (patients' doses remained stable).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataThe average effective dose of nabilone was 0.5 mg one hour before bedtime, with an effective dose range of 0.2 mg to 4.0 mg nightly.
“The average effective dose of nabilone was 0.5 mg one hour before bedtime, with an effective dose range of 0.2 mg to 4.0 mg nightly.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenPatients were carefully monitored for any adverse reactions.
“The patients were carefully monitored for any adverse reactions.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
PremisecitationThere is limited but promising evidence for prazosin and olanzapine for managing PTSD nightmares and insomnia.
“Drawing on the available data it can be concluded that there is limited but promising evidence for prazosin and olanzapine for managing PTSD nightmares and insomnia” [8].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [8] 8. Van Liempt S, Vermetten E, Geuze E, Westenberg H. Pharmacotherapeutic treatment of nightmares and insomnia in post traumatic stress disorders: An overview of the literature. Ann NY Acad Sci 2006;1071:502-507. source
Classified as probably not a substantial claim. May combine two claims.
Study design and conductnone givenThe author had to rely on subjective reports of nightmare presence and relief because no reliable test exists to objectively measure the presence or intensity of nightmares.
“The author had to rely on subjective reports of nightmare presence and subsequent relief with the use of nabilone since, at present, there is no reliable test to objectively measure the presence or intensity of nightmares.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Study design and conductnone givenEligibility for the study required a current nightmare frequency of at least once weekly.
“Eligibility for this study stipulated that current nightmare frequency was a minimum of once weekly.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataThree patients who initially responded positively to nabilone were lost to follow-up.
“Three patients, who initially responded positively, were lost to follow-up.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationThe endocannabinoid system has been implicated in the control of behaviors including eating, addiction and memory, and in mediating anxiolytic effects and pain responses.
“The endocannabinoid system has been implicated in the control of various behaviors including eating, addiction, and memory and in mediating both anxiolytic effects and pain responses [6][7][8].”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [6] 6. Ohayon M, Shapiro C. Sleep disturbances and psychiatric disorders associated with posttraumatic stress disorder in the general population. Compr Psychiatry 2000;41:469-478. source
- cites [7] 7. Krakow B, Schrader R, Tandberg D, Hollifield M, Koss MP, Yau CL, Cheng DT. Nightmare frequency in sexual assault survivors with PTSD. J Anxiety Disord 2002;16:175-190. source
- cites [8] 8. Van Liempt S, Vermetten E, Geuze E, Westenberg H. Pharmacotherapeutic treatment of nightmares and insomnia in post traumatic stress disorders: An overview of the literature. Ann NY Acad Sci 2006;1071:502-507. source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationNabilone, an endocannabinoid receptor (CB1 and CB2) agonist, has been in use in Europe and Canada for over 25 years and was recently approved in the United States for chemotherapy-induced nausea and vomiting.
“Nabilone (Cesamet; Valeant Canada, Ltd., Montreal, Canada), an endocannabinoid receptor (CB 1 and CB 2 ) agonist, has been in use in Europe and Canada for over 25 years and was recently granted approval in the United States for the treatment of chemotherapy-induced nausea and vomiting.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [12] 12. Kathuria S, Gaetani S, Fegley D, Vali ño F, Duranti A, Tontini A, Mor M, Tarzia G, La Rana G, Calignano A, et al. Modulation of anxiety through blockade of anandamide hydrolysis. Nat Med 2003;9:76-81. source
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductcitationAll nabilone doses were kept below the maximum 6 mg daily, as per the Cesamet product monograph.
“All doses were kept below the maximum 6 mg daily, as per the Cesamet (nabilone) product monograph [28].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [28] 28. CESAMET TM (nabilone) Product Monograph. Valeant Canada, Ltd. Montreal, Quebec, Canada, 2006.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationSelective serotonin reuptake inhibitors (SSRIs) are considered first-line agents in the pharmacological treatment of PTSD in the United States.
“Selective serotonin reuptake inhibitors (SSRIs) are considered first-line agents in the pharmacological treatment of PTSD in the United States (e.g., paroxetine and sertraline).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [5] 5. Friedman, M. Post-traumatic and acute stress disorders: The latest assessment and treatment strategies, 4th Edition. Kansas City: Compact Clinicals, 2006; 58-64.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Classified as probably not a substantial claim.
Study design and conductnone givenNightmares were considered treatment-resistant when they persisted despite conventional medications employed for PTSD.
“Nightmares were considered “treatment-resistant” when these persisted in spite of conventional medications employed for PTSD.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S4 (based).
Interpretationnone givenThis is the first report of the use of nabilone for the management of treatment-resistant nightmares in PTSD.
“This is the first report of the use of nabilone (Cesamet; Valeant Canada, Ltd., Montreal, Canada) for the management of treatmentresistant nightmares in PTSD.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductreasoningPrevious medications, ranging from a single SSRI to polypharmacy, were not changed during the study.
“Previous medications, which ranged from a single SSRI to polypharmacy, were not changed during the study.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S2 (checkable). May combine two claims.
PremisereasoningThere is a clinical need for a medication effective in treating PTSD-related nightmares, with positive effects on sleep and little potential for side effects or drug interaction.
“On the basis of these experiences, there is a definite clinical need for a medication that is effective in treating nightmares related to PTSD, with positive effects on sleep and little potential for side effects or drug interaction.”
Quote in the paperNot a substantial claim
The paper relies on this without support.
At therapeutic doses, nabilone does not produce the psychological high of inhaled marijuana.
“For example, at therapeutic doses, nabilone does not appear to produce the psychological high of inhaled marijuana.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In humans, the synthetic cannabinoid nabilone significantly reduces nightmares and flashbacks in patients with posttraumatic stress disorder.
“In humans, the synthetic cannabinoid nabilone significantly reduces nightmares and flashbacks in patients with posttraumatic stress disorder (Fraser, 2009).”
From Acute stress increases circulating anandamide and other N-acylethanolamines in healthy humans (2012) · cites this paper as Fraser, 2009
Synthetic cannabinoid receptor agonists or plant-derived cannabinoids such as marijuana may possess some benefits in individuals with PTSD by helping relieve haunting nightmares and other symptoms of PTSD.
“Such findings substantiate, at least in part, emerging evidence that synthetic cannabinoid receptor agonists50 or plant-derived cannabinoids such as marijuana51 may possess some benefits in individuals with PTSD by helping relieve haunting nightmares and other symptoms of PTSD.”
From Elevated brain cannabinoid CB1 receptor availability in post-traumatic stress disorder: A positron emission tomography study (2013) · cites this paper as [50]
Stimulation of EC signaling in patients with PTSD by administration of the synthetic cannabinoid nabilone resulted in an improvement of memory-related PTSD symptoms.
“a recent study demonstrated that a stimulation of EC signaling in patients with PTSD by administration of the synthetic cannabinoid nabilone resulted in an improvement of memory-related PTSD symptoms [17].”
From Plasma concentrations of endocannabinoids and related primary fatty acid amides in patients with post-traumatic stress disorder (2013) · cites this paper as [17]
Use of the synthetic cannabinoid nabilone resulted in an improvement of symptoms.
“and the use of the synthetic cannabinoid nabilone resulted in an improvement of symptoms [17].”
From Plasma concentrations of endocannabinoids and related primary fatty acid amides in patients with post-traumatic stress disorder (2013) · cites this paper as [17]
THC administration can reduce anxiety in patients with anxiety disorders.
“studies in controlled clinical settings confirm that administration of synthetic variants of delta-9-tetrahydrocannabinol (THC), the psychoactive constituent of cannabis, can reduce anxiety in patients with anxiety disorders [7,8]”
From Amygdala FAAH and anandamide: mediating protection and recovery from stress (2013) · cites this paper as [8]
In humans, the synthetic cannabinoid nabilone has demonstrated potential benefits in PTSD patients.
“In humans, potential benefits of the synthetic cannabinoid nabilone were demonstrated in PTSD patients (Fraser, 2009).”
From Cannabinoids prevent the development of behavioral and endocrine alterations in a rat model of intense stress (2012) · cites this paper as Fraser, 2009
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BackgroundSystematic Review of Body Image Measures
Kling, J., Kwakkenbos, L., Diedrichs, P. C., Rumsey, N., Frisén, A., Brandão, M. P., Silva, A. G., Dooley, B., Rodgers, R. F., & Fitzgerald, A. (2019) · Body Image · doi:10.1016/j.bodyim.2019.06.006 · Cited by 209 · see citing works
Baron, E. P. (2015) · Headache The Journal of Head and Face Pain · doi:10.1111/head.12570 · Cited by 205 · see citing works
“2 to 6 mg/day.(241,242) It is Schedule II and FDA approved for nausea/vomiting associated with chemotherapy.”
BackgroundClinical applications of hallucinogens: a review
Garcia-Romeu, A., Kersgaard, B., & Addy, P. H. (2016) · Experimental and Clinical Psychopharmacology · doi:10.1037/pha0000084 · Cited by 201 · see citing works
“Cannabinoids have also been shown to reduce traumatic nightmares in sufferers of PTSD (Fraser, 2009).”
BackgroundHauer, D., Schelling, G., Gola, H., Campolongo, P., Morath, J., Roozendaal, B., Hamuni, G., Karabatsiakis, A., Atsak, P., Vogeser, M., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0062741 · Cited by 200 · see citing works
“Interestingly, patients with PTSD often abuse cannabinoids [16] and the use of the synthetic cannabinoid nabilone resulted in an improvement of symptoms [17].”
BackgroundResultRoitman, P., Mechoulam, R., Cooper‐Kazaz, R., & Shalev, A. Y. (2014) · Clinical Drug Investigation · doi:10.1007/s40261-014-0212-3 · Cited by 202 · see citing works
“The beneficial effect of D-THC on sleep and nightmares replicates previous findings by Fraser [9], who reported on similar effects with nabilone in chronic PTSD (alleviation or cessation of nightmares).”
BackgroundResultHillard, C. J., Weinlander, K. M., & Stuhr, K. L. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.11.020 · Cited by 186 · see citing works
“A small study of the therapeutic benefit of nabilone, an CB1R agonist that is given orally, a majority of patients treated (72% of 47 patients total) experienced a significant reduction in intensity or complete elimination of nightmares (Fraser, 2009).”
BackgroundBilbao, A., & Spanagel, R. (2022) · BMC Medicine · doi:10.1186/s12916-022-02459-1 · Cited by 181 · see citing works
The role of the immune system in posttraumatic stress disorder
Katrinli, Ş., Oliveira, N. C. D. S., Felger, J. C., Michopoulos, V., & Smith, A. K. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-02094-7 · Cited by 177 · see citing works
Cameron, C., Watson, D. B., & Robinson, J. (2014) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000000180 · Cited by 171 · see citing works
“5) would be expected based on previous research.(7) Given an > error probability of 0.”
BackgroundSuraev, A. S., Marshall, N. S., Vandrey, R. G., McCartney, D., Benson, M. J., McGregor, I. S., Grunstein, R. R., & Hoyos, C. M. (2020) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2020.101339 · Cited by 162 · see citing works
The endocannabinoid system and psychiatric disorders
Parolaro, D., Realini, N., Viganò, D., Guidali, C., & Rubino, T. (2010) · Experimental Neurology · doi:10.1016/j.expneurol.2010.03.018 · Cited by 150 · see citing works
“The involvement of the eCB system and its possible exploitation has been reviewed extensively elsewhere (Fraser, 2009; Lutz, 2007).”
BackgroundPTSD Symptom Reports of Patients Evaluated for the New Mexico Medical Cannabis Program
Greer, G. R., Grob, C. S., & Halberstadt, A. L. (2014) · Journal of Psychoactive Drugs · doi:10.1080/02791072.2013.873843 · Cited by 149 · see citing works
“It has also been reported that the synthetic cannabinoid nabilone can reduce the incidence and severity of nightmares in PTSD patients (Fraser 2009).”
BackgroundBowers, M. E., & Ressler, K. J. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.06.008 · Cited by 147 · see citing works
THC and CBD: Similarities and differences between siblings
Stella, N. (2023) · Neuron · doi:10.1016/j.neuron.2022.12.022 · Cited by 149 · see citing works
Lanius, R. A., Boyd, J. E., McKinnon, M. C., Nicholson, A. A., Frewen, P., Vermetten, E., Jetly, R., & Spiegel, D. (2018) · Current Psychiatry Reports · doi:10.1007/s11920-018-0983-y · Cited by 138 · see citing works
Atsak, P., Hauer, D., Campolongo, P., Schelling, G., McGaugh, J. L., & Roozendaal, B. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1200742109 · Cited by 140 · see citing works
“Although clinical studies have not yet investigated interactions between these two stress systems, recent findings indicate that administration of the synthetic cannabinoid nabilone to PTSD patients resulted in a highly comparable reduction of treatment-resistant daytime flashbacks and nightmares (56).”
BackgroundOrsolini, L., Chiappini, S., Volpe, U., Berardis, D. D., Latini, R., Papanti, G. D., & Corkery, J. (2019) · Medicina · doi:10.3390/medicina55090525 · Cited by 135 · see citing works
“Fraser [33] reported a study examining the effect of nabilone in managing PTSD-related nightmares.”
BackgroundInfluentialMcLaughlin, R. J., Hill, M. N., & Gorzalka, B. B. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.02.006 · Cited by 130 · see citing works
Bonn‐Miller, M. O., Sisley, S., Riggs, P., Yazar‐Klosinski, B., Wang, J. B., Loflin, M., Shechet, B., Hennigan, C., Matthews, R., Emerson, A., et al. (2021) · PLoS ONE · doi:10.1371/journal.pone.0246990 · Cited by 128 · see citing works
The effects of cannabinoid administration on sleep: a systematic review of human studies
Gates, P., Albertella, L., & Copeland, J. (2014) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2014.02.005 · Cited by 127 · see citing works
“…and “details of sleep disruptions” kept in diary Age, gender, pain ratings, substance abuse 52.1% male, all suffering pain (n ¼ 96/64) Results were reported in a table as “sleep” and no drug effects were found (dose effect was unclear) Fraser 2009 [66] 20.0 US Graduating doses of nabilone (0.5e6.”
BackgroundInfluentialWei, D., Dinh, D., Lee, D., Li, D., Anguren, A., Moreno-Sanz, G., Gall, C. M., & Piomelli, D. (2016) · Cannabis and Cannabinoid Research · doi:10.1089/can.2015.0008 · Cited by 122 · see citing works
“is particularly important in light of the known roles of endocannabinoids in stress modulation.(19,30,40,41) In our case, we found that the prosocial action of ananda-”
BackgroundGanon-Elazar, E., & Akirav, I. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2011.204 · Cited by 120 · see citing works
“In humans, potential benefits of the synthetic cannabinoid nabilone were demonstrated in PTSD patients (Fraser, 2009).”
BackgroundHill, M. N., & Patel, S. (2013) · Biology of Mood & Anxiety Disorders · doi:10.1186/2045-5380-3-19 · Cited by 117 · see citing works
“Consistent with this, we have recently demonstrated that PTSD is associated with reduced levels of 2-AG in the circulation, while lower AEA levels correlated with the intensity of intrusive symptoms [116].”
BackgroundInfluentialThe use of cannabinoids for sleep: A critical review on clinical trials.
Kuhathasan, N., Dufort, A., MacKillop, J. M., Gottschalk, R., Minuzzi, L., & Frey, B. N. (2019) · Experimental and Clinical Psychopharmacology · doi:10.1037/pha0000285 · Cited by 105 · see citing works
Effects of Cannabinoids on Sleep and their Therapeutic Potential for Sleep Disorders
Kaul, M., Zee, P. C., & Sahni, A. (2021) · Neurotherapeutics · doi:10.1007/s13311-021-01013-w · Cited by 109 · see citing works
Is cannabis treatment for anxiety, mood, and related disorders ready for prime time?
Turna, J., Patterson, B. A., & Ameringen, M. V. (2017) · Depression and Anxiety · doi:10.1002/da.22664 · Cited by 101 · see citing works
“Most experienced a recurrence of nightmares when nabilone was discontinued, but responded once reinitiated (Fraser, 2009).”
BackgroundGanon-Elazar, E., & Akirav, I. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.01.014 · Cited by 98 · see citing works
“…interest directed at the pharmacological properties of cannabinoids as a possible treatment of stressand anxiety-related disorders such as post-traumatic stress disorder (PTSD) (Fraser, 2009; Ganon-Elazar and Akirav, 2009; Abush and Akirav, 2010; Akirav, 2011; Ganon-Elazar and Akirav, 2012).”
BackgroundBelendiuk, K. A., Baldini, L., & Bonn‐Miller, M. O. (2015) · Addiction Science & Clinical Practice · doi:10.1186/s13722-015-0032-7 · Cited by 96 · see citing works
“Though the use of marijuana and oral THC [104,105] have been implicated as a potential mechanism for the mitigation of many PTSD symptoms byway of their effects on the endocannabinoid system, some researchers caution that endocannabinoid activation with plant-based extracts over extended periods may lead to a number o…”
BackgroundInfusion of cannabidiol into infralimbic cortex facilitates fear extinction via CB1 receptors
Monte, F. H. D., de Souza, R. R., de Bitencourt, R. M., Kroon, J. A. V., & Takahashi, R. N. (2013) · Behavioural Brain Research · doi:10.1016/j.bbr.2013.04.045 · Cited by 88 · see citing works
Multilevel Interactions of Stress and Circadian System: Implications for Traumatic Stress
Agorastos, A., Nicolaides, N. C., Bozikas, V. P., Chrousos, G. P., & Pervanidou, P. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.01003 · Cited by 89 · see citing works
Latest advances in cannabinoid receptor agonists
Thakur, G. A., Tichkule, R. B., Bajaj, S., & Makriyannis, A. (2009) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543770903436505 · Cited by 87 · see citing works
“Recently, nabilone has also been evaluated successfully for the management of treatment-resistantnightmares inposttraumatic stressdisorder [51].”
BackgroundBotsford, S. L., Yang, S., & George, T. P. (2020) · The American Journal on Addictions · doi:10.1111/ajad.12963 · Cited by 88 · see citing works
Kamprath, K., Romo-Parra, H., Häring, M., Gaburro, S., Doengi, M., Lutz, B., & Pape, H.-C. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2010.196 · Cited by 86 · see citing works
“…reported a reduction of otherwise treatment-resistant nightmares in PTSD patients upon treatment with a synthetic endocannabinoid receptor agonist (Fraser, 2009), which is supported by an analysis of single-nucleotide polymorphisms in the CNR1 gene suggesting a possible association with PTSD (Lu…”
MethodTrezza, V., & Campolongo, P. (2013) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2013.00100 · Cited by 84 · see citing works
“%) receiving nabilone experienced either cessation of nightmares or a significant reduction in nightmare intensity (Fraser, 2009).”
BackgroundFrom endocannabinoid profiling to ‘endocannabinoid therapeutics’
Ligresti, A., Petrosino, S., & Marzo, V. D. (2009) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2009.04.615 · Cited by 85 · see citing works
Choi, K. H., Le, T., McGuire, J. L., Xing, G., Zhang, L., Li, H., Parker, C. C., Johnson, L. R., & Ursano, R. J. (2012) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2012.03.021 · Cited by 83 · see citing works
The effects of trauma on brain and body: A unifying role for the midbrain periaqueductal gray
Terpou, B. A., Harricharan, S., McKinnon, M. C., Frewen, P., Jetly, R., & Lanius, R. A. (2019) · Journal of Neuroscience Research · doi:10.1002/jnr.24447 · Cited by 82 · see citing works
“…psychoactive com‐ ponent of marijuana, tetrahydrocannabinol (THC), that acts on the endocannabinoid system, has revealed reduced nightmares and symptom severity in persons with PTSD following administration (Cameron, Watson, & Robinson, 2014; Fraser, 2009; Jetly, Heber, Fraser, & Boisvert, 2015).”
BackgroundUse and effects of cannabinoids in military veterans with posttraumatic stress disorder
Betthauser, K. D., Pilz, J., & Vollmer, L. E. (2015) · American Journal of Health-System Pharmacy · doi:10.2146/ajhp140523 · Cited by 78 · see citing works
Benefits and Harms of Plant-Based Cannabis for Posttraumatic Stress Disorder
O'Neil, M. E., Nugent, S. M., Morasco, B. J., Freeman, M., Low, A., Kondo, K. K., Zakher, B., Elven, C., Motu’apuaka, M. L., Paynter, R. A., et al. (2017) · Annals of Internal Medicine · doi:10.7326/m17-0477 · Cited by 76 · see citing works
“In the second review, Walsh and colleagues (19) evaluated 4 observational studies of synthetic and nonsynthetic cannabis preparations that reported on PTSD symptoms (20, 24, 27, 29).”
BackgroundCross, D., Crow, T., Powers, A., & Bradley, B. (2015) · Child Abuse & Neglect · doi:10.1016/j.chiabu.2015.01.007 · Cited by 76 · see citing works
Berardi, A., Schelling, G., & Campolongo, P. (2016) · Pharmacological Research · doi:10.1016/j.phrs.2016.07.024 · Cited by 75 · see citing works
Medicinal versus recreational cannabis use among returning veterans.
Metrik, J., Bassett, S. S., Aston, E. R., Jackson, K. M., & Borsari, B. E. (2018) · Translational Issues in Psychological Science · doi:10.1037/tps0000133 · Cited by 75 · see citing works
“…on effectiveness of MC as PTSD treatment is currently lacking, preliminary research indicates cannabinoid receptor agonists to have beneficial effects in terms of relief from PTSD symptoms (Fraser, 2009; Jetly, Heber, Fraser, & Boisvert, 2015; Roitman, Mechoulam, Cooper-Kazaz, & Shalev, 2014).”
Cannabinoid interventions for PTSD: Where to next?
Ney, L. J., Matthews, A. J., Bruno, R., & Felmingham, K. L. (2019) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2019.03.017 · Cited by 76 · see citing works
Neumeister, A., Seidel, J., Ragen, B., & Pietrzak, R. H. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.10.012 · Cited by 76 · see citing works
“They authenticate, at least in part, emerging evidence that synthetic cannabinoid receptor agonists (Fraser, 2009) or plant-derived cannabinoids such as marijuana (Passie et al., 2012) may possess some benefits in individuals with PTSD by helping relieve haunting nightmares and other threat-related…”
BackgroundSteenkamp, M. M., Blessing, E., Galatzer‐Levy, I. R., Hollahan, L., & Anderson, W. T. (2017) · Depression and Anxiety · doi:10.1002/da.22596 · Cited by 75 · see citing works
“Almost twothirdsof participants (72%)experiencedeither cessationofnightmares or a significant reduction in nightmare intensity, and reported subjective improvements in sleep (Fraser, 2009).”
BackgroundThe influence of cannabinoids on learning and memory processes of the dorsal striatum
Goodman, J., & Packard, M. G. (2015) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2015.06.008 · Cited by 74 · see citing works
“Recent studies have suggested that cannabinoids may be used to treat the emotional and cognitive symptoms of PTSD (Fraser, 2009; Neumeister et al., 2015; Passie, Emrich, Karst, Brandt, & Halpern, 2012; Rabinak & Phan, 2014; Trezza & Campolongo, 2013).”
BackgroundInfluentialTreatment-refractory posttraumatic stress disorder (TRPTSD): a review and framework for the future
Koek, R. J., Schwartz, H. N., Scully, S., Langevin, J., Spangler, S. L., Korotinsky, A., Jou, K., & Leuchter, A. F. (2016) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2016.01.015 · Cited by 70 · see citing works
Failure to extinguish fear and genetic variability in the human cannabinoid receptor 1
Heitland, I., Klumpers, F., Oosting, R. S., Evers, D. J. J., Kenemans, J. L., & Baas, J. M. P. (2012) · Translational Psychiatry · doi:10.1038/tp.2012.90 · Cited by 69 · see citing works
Endocannabinoids and Mental Disorders
Rubino, T., Zamberletti, E., & Parolaro, D. (2015) · Handbook of experimental pharmacology · doi:10.1007/978-3-319-20825-1_9 · Cited by 71 · see citing works
Chronic treatment with URB597 ameliorates post-stress symptoms in a rat model of PTSD
Fidelman, S., Zer‐Aviv, T. M., Lange, R., Hillard, C. J., & Akirav, I. (2018) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2018.02.004 · Cited by 67 · see citing works
“Recent clinical (Fraser, 2009; Hauer et al., 2013; Roitman et al., 2014) and preclinical studies (Ganon-Elazar and Akirav, 2012; Hill et al., 2018; Trezza and Campolongo, 2013) implicate the eCB system as a possible therapeutic target to treat both the emotional and cognitive dysfunctions…”
Management of nightmares in patients with posttraumatic stress disorder: current perspectives
El-Solh, A. (2018) · Nature and Science of Sleep · doi:10.2147/nss.s166089 · Cited by 69 · see citing works
“47 patients with at least a 2-year history of PTSD-related nightmares.(118) Patients was started at 0.”
BackgroundRaut, S. B., Marathe, P. A., van Eijk, L., Eri, R. D., Ravindran, M., Benedek, D. M., Ursano, R. J., Canales, J. J., & Johnson, L. R. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108195 · Cited by 71 · see citing works
Developmental regulation of fear learning and anxiety behavior by endocannabinoids
Lee, T. T.-Y., Hill, M. N., & Lee, F. S. (2015) · Genes Brain & Behavior · doi:10.1111/gbb.12253 · Cited by 67 · see citing works
“…(Green et al. 2003; Hunault et al. 2014; Temple et al. 2014) and in patients with an anxiety disorder (Crippa et al. 2011; Fabre & McLendon 1981; Fraser 2009; 108 © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society Jetly et al. 2015; Nakano et al. 1978;…”
Ney, L., Matthews, A., Bruno, R., & Felmingham, K. (2018) · Neuroscience and Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.07.006 · Cited by 65 · see citing works
“Early studies have found that systematic cannabinoid administration has been shown to improve treatment-resistant nightmares in PTSD patients (Cameron et al., 2014; Fraser, 2009; Jetly et al., 2015), and cannabis is often used by PTSD patients to self-manage symptoms (Steenkamp et al.”
BackgroundSleep in Psychiatric Disorders: Where are We Now?
Lee, E. K., & Douglass, A. B. (2010) · The Canadian Journal of Psychiatry · doi:10.1177/070674371005500703 · Cited by 66 · see citing works
“These findings have led investigators to use nabilone, a synthetic cannabinoid, for mitigating PTSD nightmares with some reported success.(84) Cannabis withdrawal has been associated with sleep disturbances, with disturbing dreams most consistently reported.”
BackgroundHaney, M., & Evins, A. E. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.251 · Cited by 64 · see citing works
Cannabinoids and glucocorticoids modulate emotional memory after stress
Akirav, I. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.08.002 · Cited by 64 · see citing works
Targeting the endocannabinoid system to treat anxiety-related disorders
Korem, N., Zer‐Aviv, T. M., Ganon-Elazar, E., Abush, H., & Akirav, I. (2015) · Journal of Basic and Clinical Physiology and Pharmacology · doi:10.1515/jbcpp-2015-0058 · Cited by 64 · see citing works
Psychobiological Responses to Aerobic Exercise in Individuals With Posttraumatic Stress Disorder
Crombie, K. M., Brellenthin, A. G., Hillard, C. J., & Koltyn, K. F. (2018) · Journal of Traumatic Stress · doi:10.1002/jts.22253 · Cited by 65 · see citing works
Hindocha, C., Cousijn, J., Rall, M., & Bloomfield, M. (2019) · Journal of Dual Diagnosis · doi:10.1080/15504263.2019.1652380 · Cited by 64 · see citing works
“Fraser (2009) investigated nabilone in an open-label clinical trial in 47 patients with PTSD treatment-resistant nightmares.”
BackgroundDopamine, endocannabinoids and their interaction in fear extinction and negative affect in PTSD
Ney, L. J., Akhurst, J., Bruno, R., Laing, P. A. F., Matthews, A. J., & Felmingham, K. L. (2020) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.110118 · Cited by 61 · see citing works
Short and Long-Term Effects of Cannabis on Symptoms of Post-Traumatic Stress Disorder
LaFrance, E. M., Glodosky, N. C., Bonn‐Miller, M. O., & Cuttler, C. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.05.132 · Cited by 59 · see citing works
Korem, N., & Akirav, I. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.132 · Cited by 58 · see citing works
Sex differences in hippocampal response to endocannabinoids after exposure to severe stress
Zer‐Aviv, T. M., & Akirav, I. (2016) · Hippocampus · doi:10.1002/hipo.22577 · Cited by 58 · see citing works
Therapeutic Uses of Cannabis on Sleep Disorders and Related Conditions
Choi, S., Huang, B. C., & Gamaldo, C. E. (2019) · Journal of Clinical Neurophysiology · doi:10.1097/wnp.0000000000000617 · Cited by 56 · see citing works
Campos, A. C., Ferreira, F. R., Silva, W. A., & Guimarães, F. S. (2012) · Neuroscience Letters · doi:10.1016/j.neulet.2012.11.016 · Cited by 56 · see citing works
Clinical Data for the Use of Cannabis-Based Treatments: A Comprehensive Review of the Literature
Inglet, S., Winter, B., Yost, S. E., Entringer, S., Lian, A., Biksacky, M., Pitt, R. D., & Mortensen, W. (2020) · Annals of Pharmacotherapy · doi:10.1177/1060028020930189 · Cited by 53 · see citing works
Krediet, E., Janssen, D. G. A., Heerdink, E. R., Egberts, T. C. G., & Vermetten, E. H. G. J. M. (2020) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2020.04.009 · Cited by 56 · see citing works
“Several studies have reported improvements in PTSD symptoms with the use of cannabis ( Greer et al., 2014 ; Passie et al., 2012 ; Reznik, 2012 ), oral THC ( Roitman et al., 2014 ), and the synthetic cannabinoid nabilone ( Cameron et al., 2014 ; Fraser, 2009 ; Jetly et al., 2015 ).”
The Endocannabinoid System and Anxiety
Lisboa, S. F. D. S., Gomes, F. V., Terzian, A. L. B., de Aguiar, D. C., Moreira, F. A., Resstel, L. B. M., & Guimarães, F. S. (2016) · Vitamins and hormones · doi:10.1016/bs.vh.2016.09.006 · Cited by 56 · see citing works
Therapeutic potential of medicinal marijuana: an educational primer for health care professionals
Mouhamed, Y., Vishnyakov, A., Qorri, B., Sambi, M., Frank, S. M. S., Nowierski, C., Lamba, A., Bhatti, U., & Szewczuk, M. R. (2018) · Drug Healthcare and Patient Safety · doi:10.2147/dhps.s158592 · Cited by 56 · see citing works
“effect of nabilone on helping with PTSD-associated nightmares.(190) Of the patients with treatment-refractory night-”
Bowers, M. E., & Ressler, K. J. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.225 · Cited by 54 · see citing works
“Indeed, a synthetic cannabinoid has recently been shown to reduce treatment-resistant nightmares in a majority of PTSD patients (Fraser, 2009).”
Sleep Disorders in Patients With Posttraumatic Stress Disorder
El-Solh, A., Riaz, U., & Roberts, J. (2018) · CHEST Journal · doi:10.1016/j.chest.2018.04.007 · Cited by 53 · see citing works
Thieme, U., Schelling, G., Hauer, D., Greif, R. T., Dame, T., Laubender, R. P., Bernhard, W. R., Thieme, D., Campolongo, P., & Theiler, L. G. (2013) · Drug Testing and Analysis · doi:10.1002/dta.1561 · Cited by 50 · see citing works
Nightmares and Posttraumatic Stress Disorder (PTSD)
Campbell, R. L., & Germain, A. (2016) · Current Sleep Medicine Reports · doi:10.1007/s40675-016-0037-0 · Cited by 52 · see citing works
Loflin, M., Earleywine, M., & Bonn‐Miller, M. O. (2017) · Addictive Behaviors · doi:10.1016/j.addbeh.2017.01.008 · Cited by 48 · see citing works
Cannabinoids as therapeutics for PTSD
Sbarski, B., & Akirav, I. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107551 · Cited by 47 · see citing works
Treatment Options for Parasomnias
Attarian, H. P. (2010) · Neurologic Clinics · doi:10.1016/j.ncl.2010.03.025 · Cited by 46 · see citing works
Involvement of the GABAergic system in PTSD and its therapeutic significance
Huang, J., Xu, F., Yang, L.-P., Tuolihong, L., Wang, X., Du, Z., Zhang, Y., Yin, X., Li, Y.-J. D., Lu, K., et al. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1052288 · Cited by 41 · see citing works
“The agonists of CB1 such as nabilone and M9-THC can relieve some of the clinical symptoms of PTSD, such as over-stress, forgetfulness, nightmares, and pain (Bremner et al., 1996; Fraser, 2009; Passie et al., 2012).”
BackgroundWaltman, S. H., Shearer, D. S., & Moore, B. A. (2018) · Current Psychiatry Reports · doi:10.1007/s11920-018-0971-2 · Cited by 46 · see citing works
Suraev, A. S., Grunstein, R. R., Marshall, N. S., D'Rozario, A. L., Gordon, C. J., Bartlett, D. J., WONG, K. K. H., Yee, B. J., Vandrey, R. G., Irwin, C. G., et al. (2020) · BMJ Open · doi:10.1136/bmjopen-2019-034421 · Cited by 45 · see citing works
“…studies using synthetic THC (nabilone) showed improvements in subjective sleep quality in patients with post-traumatic stress disorder (PTSD) 54 55 and fibromyalgia, 56 while CBD was found to be effective in reducing the frequency of rapid eye movement sleep behaviour disorder events in…”
Spanagel, R., & Bilbao, A. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108680 · Cited by 43 · see citing works
“…Glass et al., 1981; Jones et al., 1982; George et al., 1983; Cunningham et al., 1985, 1988, 1988; Niiranen and Mattson, 1987; Sieradzan et al., 2001; Fraser, 2009; Herrmann et al., 2016; Peball et al., 2019; Ruthirakuhan et al., 2020; Kayser et al., 2020) which did not meet our inclusion criteria…”
BackgroundZer‐Aviv, T. M., Segev, A., & Akirav, I. (2016) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000253 · Cited by 43 · see citing works
“coping motives), very little research has been carried out to examine specifically whether PTSD symptoms are indeed reduced with cannabinoids (Fraser, 2009; Roitman et al., 2014; Jetly et al., 2015).”
BackgroundProspects for the Use of Cannabinoids in Psychiatric Disorders
Graczyk, M., Łukowicz, M., & Dzierżanowski, T. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.620073 · Cited by 45 · see citing works
- Authors
- Fraser, G. A.
- Affiliations
- Canadian Armed Forces (CA)
- Corresponding author
- Fraser, George A.
- Venue
- CNS Neuroscience & Therapeutics
- Publisher
- Wiley
- Published
- 2009-02-13
- Volume
- 15
- Issue
- 1
- Pages
- 84-88
- ISSN
- 1755-5930 (ISSN-L)
- 1755-5949
- PMC
- PMC6494011
- OpenAlex
- W2019432331
- Semantic Scholar
- b314e6338c8468983f092432a6081353c1c73444
- Cited by
- 283
- References
- 28
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 14 · 2023: 17 · 2022: 29 · 2021: 19 · 2020: 27 · 2019: 23 · 2018: 24 · 2017: 18 · 2016: 16 · 2015: 22 · 2014: 16 · 2013: 12 · 2012: 12
- FWCI
- 10.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- CNS Neuroscience & Therapeutics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Keywords
- nabilone, post-traumatic stress disorder, nightmares, synthetic cannabinoids, adjunctive pharmacotherapy, sleep quality, flashbacks
- MeSH terms
- Adult, Aged, Cannabinoids, Dreams, Drug Resistance, Female, Humans, Male, Middle Aged, Stress Disorders, Post-Traumatic
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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