Abstract
Introduction: The synthetic cannabinoid nabilone has shown promise in the management of posttraumatic stress disorder (PTSD) nightmares. To date, three clinical papers have been published showing positive results in nightmare suppression in civilian and military populations. This medication came on the market as an antiemetic. Nabilone has been used on an off-label basis at the Canadian Forces Operational Trauma and Stress Support Centre (OTSSC) in Ottawa for over a decade for PTSD nightmares. To date, there are no published reports of the ongoing experiences of patients who have been prescribed this medication for nightmare suppression. This research was conducted with the intent to fill this gap in the literature. Methods: An anonymous online survey was conducted in order to obtain a better understanding of the clinical effects experienced by those who continued taking nabilone. Eligible participants were active military members diagnosed with PTSD who were prescribed nabilone for the suppression of chronic nightmares. Results: Sixty military members responded to questions related to their ongoing experience using nabilone. Prior to taking nabilone, they had suffered from PTSD nightmares for an average of seven years. Suppression of nightmares was reported by 73% of respondents who continued taking nabilone. A small proportion self-discontinued nabilone to determine whether the medication was still needed. Of those who discontinued, most reported a return of nightmares an average of 1 week later; however, not all experienced a recurrence of nightmares. These findings support attempting a reduction or cessation at some point during treatment. For those who continued to experience nightmares, suppression was achieved with similar dosages to those previously prescribed; this suggests that nightmares are chronic and may need a longer duration of treatment. Discussion: This is the first survey to capture data for nabilone as a PTSD nightmare treatment beyond seven weeks. The results of this survey conform to the existing literature showing the efficacy of nabilone, a synthetic cannabinoid, as having a positive effect on nightmare suppression.
Introduction : La nabilone, un cannabinoïde synthétique, est prometteur pour la prise en charge des cauchemars causés par un état de stress post-traumatique (ÉSPT). Jusqu’à présent, trois articles cliniques publiés en ont démontré les résultats positifs sur la suppression des cauchemars au sein des populations civiles et militaires. Ce médicament a été mis en marché sous forme d’antiémétique. Depuis plus d’une décennie, les Centres de soutien pour trauma et stress opérationnels (CSTSO) des Forces armées canadiennes recourent à la nabilone dans un emploi conforme ou non conforme à l’étiquette pour traiter les cauchemars causés par l’ÉSPT. Jusqu’à présent, aucun rapport publié ne porte sur les expériences continues des patients à qui on a prescrit ce médicament pour supprimer les cauchemars. Le présent article a été rédigé pour corriger cette lacune. Méthodologie : Les chercheurs ont réalisé un sondage anonyme en ligne pour mieux comprendre les effets cliniques de la nabilone en continu. Les participants admissibles étaient des militaires actifs présentant un ÉSPT diagnostiqué qui avaient reçu une ordonnance de nabilone pour traiter des cauchemars chroniques. Résultats : Soixante militaires ont répondu à des questions sur leur expérience continue de la nabilone. Avant de commencer à en prendre, ils avaient souffert de cauchemars causés par l’ÉSPT pendant une période moyenne de sept ans. La prise continue de nabilone a favorisé la suppression des cauchemars chez 73% des répondants. Quelques répondants ont décidé d’eux-mêmes d’arrêter leur traitement pour vérifier s’ils en avaient encore besoin. La plupart d’entre eux, mais pas tous, ont constaté la reprise des cauchemars en moyenne une semaine plus tard. Ces observations appuient l’idée de tenter de réduire la médication ou d’y mettre un terme à un moment ou un autre du traitement. Ceux qui ont recommencé à faire des cauchemars ont pu s’en débarrasser en recommençant à prendre des doses semblables aux précédentes. Ainsi, les cauchemars seraient chroniques et pourraient nécessiter un traitement de plus longue durée. Discussion : Ce sondage est le premier à saisir des données sur la nabilone pour traiter les cauchemars causés par l’ÉSPT au-delà de sept semaines. Les résultats confirment les publications démontrant l’effet positif de la nabilone, un cannabinoïde synthétique, sur la suppression des cauchemars.
A cumulative incidence study of posttraumatic stress disorder (PTSD) and other mental disorders was conducted by the Canadian Armed Forces (CAF). Results indicate that 8% of service members deployed to Afghanistan received a diagnosis of PTSD.1 One of the enduring symptoms of PTSD is disabling and prolonged nightmares.
The current pharmacologic treatment options for PTSD are non-specific, and at best, have partial efficacy regarding some of the known symptom clusters of this disorder. Current treatment options do not adequately treat the intrusion phenomena, such as nightmares, though some success has been reported with use of prazosin, which has been used by the American military.2,3 In contrast to those findings, the New England Journal of Medicine published a study in 2018 on Veterans with chronic PTSD and frequent nightmares. The results of this 26-week trial failed to show a benefit of prazosin over placebo in reducing the frequency and intensity of trauma-related nightmares.4 Marijuana was legalized in Canada on October 17, 2018, under the Cannabis Act (Bill C-45), and it is legal in some U.S. states; therefore, there may be a role for cannabis as a possible agent in the treatment of PTSD, although studies might be needed. In the existing literature, a 2014 article by Roitman et al. reported that using 5 mg Δ-9 tetrahydrocanabinol (THC) showed a global improvement in PTSD symptoms and noted that it was well tolerated. This article references previous work by an author of our article, noting that the beneficial effects of Δ-9 THC on sleep and nightmares reflects previous findings by Fraser who reported on similar effects with nabilone in chronic PTSD.5
Nabilone is an option for persistent PTSD-related nightmares. This synthetic cannabinoid acts on the endocannabinoid system. The role of the endocannabinoid system in the central nervous system may hold important ramifications for the understanding and treatment of PTSD.6,7 Nabilone was initially found to be successful in managing severe nausea in cancer patients undergoing chemotherapy.8 It has also been used on an off-label basis for neuropathic pain9and has been successfully used off-label in Canada since 2004 for PTSD nightmares. Anecdotal evidence on a cohort of 47 patients first suggested a role for this medication in the management of treatment-resistant nightmares in PTSD.10 Following this, a retrospective study11 and a randomized, double-blind, placebo-controlled crossover design study12 also showed that nabilone was useful for managing PTSD-related nightmares. Nabilone is currently prescribed in the CAF for patients diagnosed with PTSD who experience disruptive ongoing nightmares. Although supported by clinical observations, there is, to the knowledge of the authors, no data supporting the long-term efficacy once treatment has been initiated.13
Nabilone was designed as a synthetic cannabinoid. It does not test positive in urine tests for THC, there is no history of dependence, nor is there a significant euphoric effect. Additionally, there is no street value or reports of lethal overdoses.14
The objective of the survey was to obtain a better understanding of the clinical effects experienced by those who continued taking nabilone. The authors were primarily interested in finding out what happened over time to the dose, therapeutic effects, and side effects. They wanted to know if nabilone had been discontinued for any reason. Inquiries were made regarding driving and any concerns about its relation to cannabis. An open-ended question about personal experiences while taking nabilone was included.
All eligible participants were active military members diagnosed with PTSD who had chronic nightmares and had been prescribed nabilone. The target population were patients (n = 150) who had been prescribed nabilone at the Ottawa Operational Trauma and Stress Support Centre (OTSSC) in the past three years. Recruiting was done through posters as well as small business cards at the Canadian Forces Health Services Centre, Ottawa. Individuals self-identified and participated by choice. No individual recruiting was done. A secure Canadian version of FluidSurveys (now part of SurveyMonkey, http://fluidsurveys.com/) was used and participants were directed to complete the anonymous online survey through the site. Questions were posed in a multiple-choice format consisting of 22 questions. Respondents were not obliged to answer all the questions, resulting in a variable number of responses. A modified Clinical Global Impression Scale was used to estimate the therapeutic effect and the side-effect load.15 There was no compensation or remuneration of any type for those who participated. The survey took place over a nine-month period.
The survey was endorsed by the Surgeon General’s Health Research Program and Ethics approval was granted by the Defence Research and Development Canada (DRDC) Human Research Ethics Committee (HREC).
Based on an estimate of 150 patients who were prescribed nabilone, 60 patients completed the survey. All were receiving evidence-based treatment for PTSD consisting of psychotropic medications and psychotherapy. Of the 60 respondents, 53 were still taking nabilone. Although seven patients had stopped treatment prior to the survey, they did complete the survey. Thirteen patients also stopped treatment in order to determine whether they still needed it. Those who stopped were asked further questions about their experience with discontinuation of the drug. Twelve of 13 who stopped the medication after a period of success had a recurrence of nightmares. Those who discontinued the medication reported a return of nightmares an average of one week later, with the earliest return of nightmares one night after cessation. When the medication was restarted, nightmare suppression was achieved with similar dosages to those previously prescribed. A return of nightmares suggests that nabilone acts primarily to suppress nightmares and may need to be continued. However, since not all experienced a recurrence of nightmares, this supports attempting a reduction or cessation at some point during treatment. The recurrence of nightmares following cessation of treatment suggests that nightmares are chronic and may need a longer duration of treatment.
The length of nabilone treatment varied, ranging from less than six months to greater than 24 months, at the time of the survey. Half of the respondents had taken it for less than a year and the remaining half had been taking it for more than a year (see Table 1).
|
| Total number of responses | 58 |
|---|---|
| Length of treatment (months) | No. (%) |
| < 6 | 19 (33) |
| 6–12 | 10 (17) |
| 12–24 | 20 (34) |
| > 24 | 9 (16) |
Prior to starting nabilone, the average length of occurrence of PTSD nightmares in our sample was seven years (SD = 7.15, median = 5, range = 35, n = 60). An average of seven years suggests that nightmares are chronic and difficult to treat. The average dose of nabilone was 2.46 mg (SD = 1.76, median = 2, range = 7.5, n = 51). The dose ranged from 0.5 mg to 8 mg. We noted an average higher dose for those who had been on it longer. The issue of tolerance could not be determined due to the limits of the survey design.
When respondents were asked how they would currently rate the effect of nabilone on their nightmares, the majority (73%) reported a marked improvement in their symptoms, with complete, or nearly complete, remission of all symptoms as rated, according to the Clinical Global Impressions (CGI) scale. The majority of the remaining respondents reported a moderate improvement, while a smaller number noted minimal or slight improvement. None of the respondents felt their symptoms were either unchanged or worse (see Table 2).
|
| Total number of replies | 52 |
|---|---|
| Therapeutic effect | No. (%) |
| Marked – Vast improvement. Complete or nearly complete remission of all symptoms | 38 (73) |
| Moderate – Decided improvement. Partial remission of symptoms | 13 (25) |
| Minimal – Slight improvement which doesn’t alter status of care of patient | 1 (2) |
| Unchanged or worse | 0 |
Regarding side effects, 25% of respondents reported none. The majority reported mild but tolerable side effects (46%); and a few (8%) attributed side effects that interfered with their functioning (see Table 3).
|
| Total number of replies | 52 |
|---|---|
| Side effects | No. (%) |
| None | 13 (25) |
| Mild and tolerable | 24 (46) |
| Moderate but not interfering with functioning | 11 (21) |
| Important and interfering with functioning | 4 (8) |
Other notable benefits related to the use of nabilone were reported by the 52 respondents; individuals were given the opportunity to report on more than one benefit. Forty of the respondents reported less or no night sweats, 33 reported better sleep, and 19 reported fewer or no flashbacks. Better mood was reported by 13 respondents and 8 individuals were able to decrease or stop other medications. A smaller number of individuals reported better pain control (6) as well as reduced anxiety (3) (see Table 4).
|
| Total number of replies | 52 |
|---|---|
| Benefit(s)* | No. |
| Less or no night sweats | 40 |
| Better sleep | 33 |
| Less or no flashbacks | 19 |
| Better mood | 13 |
| Able to decrease or stop other meds | 8 |
| Better pain control | 6 |
| Better pain control | 3 |
| No other benefit | 3 |
| Other benefits | 3 |
*Multiple choices allowed
When asked whether their use of nabilone impaired their ability to drive a vehicle, the majority answered “no.” An analysis of survey responses showed that none of those who reported impairment in driving needed to discontinue nabilone. If there are concerns about impairment, the patient should be advised to discuss this with their practitioner. Options may include taking the medication earlier in the evening, dose adjustment or discontinuation of the medication. In our survey, none of the respondents discontinued nabilone due to driving concerns.
When asked if they had concerns about nabilone and its possible relation to cannabis, the majority of respondents answered “no.” When clinicians introduce the use of nabilone, it is important to clarify that it is a synthetic cannabinoid, and not marijuana. The authors did not inquire about the concomitant use of other cannabinoids, particularly smoked marijuana, and acknowledge this limitation and recognize this as a potential confounder. All members had been asked about drug use as part of the comprehensive evaluation at the clinic before starting nabilone, however, as legalization in Canada was pending at the time this survey was conducted, the authors did not feel that self-reported marijuana use was a reliable indicator, given that its use is strictly prohibited in serving members. The Cannabis Act legalized recreational use nationally in Canada, effective October 17, 2018. The current study was completed shortly before the Act came into effect.
Of interest to the surveyors was whether there was ever a time that the respondents stopped taking nabilone. At the time of the survey, 7 of 60 respondents had already stopped nabilone prior to taking the survey. Reasons for discontinuation were mainly “strong side effects” or “no longer working.” Because it was unknown how long patients needed to remain on nabilone, it was suggested that patients could try to discontinue the medication after six months of cessation of nightmares to see if it was still needed; however, this was based on clinical experience and not guided by current evidence.
This is the first survey to capture data for nabilone as a PTSD nightmare treatment when used beyond seven weeks. The results of this survey conform to the existing literature showing the efficacy of nabilone, a synthetic cannabinoid, as having a positive effect on nightmare suppression. A total of 73% of the 52 respondents who continued nabilone reported having complete, or nearly complete, remission of all nightmares. This is almost identical to the 72% response rate reported in the 2009 article by Fraser.10 A high number also reported reduced night sweats, improved sleep, and decreased flashbacks. In general, nabilone has been reported to be well tolerated with minimal reported side effects.13 Consideration should be given for use as an adjunctive medication in the management of PTSD when nightmares persist.
Although this survey did not provide information about how long patients must remain on this medication, an average of seven years’ duration of nightmares was reported prior to commencing treatment, which highlights the chronicity of PTSD nightmares.
The authors acknowledge several limitations to the study. These include the use of a survey format and the small number of respondents. The results of this survey are non-generalizable to non-combat related PTSD nightmares, however, results from earlier studies have shown positive effects on civilian populations treated for PTSD nightmares.8,9 Active serving members of the CAF were included in the study, but it is suspected that Veterans who have released may report similar experiences with the ongoing use of nabilone. The intent was to conduct the survey by telephone in order to reach those who had released from the military and had continued use of nabilone for a longer duration than those who may be captured in the survey; however, concerns regarding confidentiality precluded this approach. As such, only patients who were still in active care could be accessed, and therefore the methodology was subsequently changed to obtaining responses via an anonymous online survey. The authors acknowledge that the current study design and informal reporting of results precluded formal statistical analyses and further elaboration of findings.
The authors note that participants continued to engage in other traditional therapies, including medications and psychotherapies, which may have had some effect on nightmare reduction.
To obtain further information on longer-term use, future studies are needed to replicate the data in those who continue to take nabilone longer term. As participants reported reductions or cessation in other PTSD symptoms with nabilone, quantifying changes in other parameters in future studies would be of interest. It would be beneficial to obtain a larger sample and to include both Veteran and civilian populations. Other future directions include studies looking at response to nabilone for non-combat PTSD nightmares. Given current existing literature on the use of prazosin for PTSD-related nightmares, a future study comparing prazosin and nabilone would be of interest. Finally, with the legalization of marijuana, it may be possible to conduct future studies comparing nabilone to cannabis for PTSD.
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All authors conceived, designed, researched, and drafted the manuscript and approved the final version submitted for publication.
The study protocol was approved by the Defence Research and Development Canada (DRDC) Human Research Ethics Committee (HREC), Ottawa, Ontario, Canada.
ACKNOWLEDGEMENTS
This study was supported by the Canadian Forces Surgeon General Health Research Program. The authors thank Col. Rakesh Jetly, CD, OMM, MD, FRCPC, from the Canadian Forces Health Services Directorate of Mental Health & Chair of Military Mental Health at The Royal Ottawa Hospital for his support with this project. Additionally, we would like to thank the Pharmacy Team at the Canadian Forces Health Services Centre (Ottawa) for their ongoing collaboration and their expertise as a resource for the use of nabilone in our survey participants.
