cbd for ptsd nightmares

December 15, 2021 By admin Off

All pre-treatment and post-treatment measures exhibited a significant improvement. Hours slept increased from 5.0 ± 1.4 (mean ± SD) to 7.2 ± 0 .2 (p<0.001), number of nights with nightmares per week decreased from 5.2 ± 2.2 to 0.9 ± 1.8 (p<0.001), and 89.6% of the participants reported improvement in their chronic pain. Improvements in sleep time, quality, and nightmares were typically seen within the first 1–2 weeks of treatment and were maintained for the entirety of the study. The Posttraumatic Checklist-Civilian score (PCL-C) also decreased significantly, from 54.7 ± 13.0 to 38.8 ± 7.1 (p=0.001), which matched a change of moderate PTSD symptoms to borderline mild. The Global Assessment of Function (GAF) also increased significantly, from 45.0 ± 6.9 to 58.2 ± 8.4 (p=0.001), which matched a change of serious to moderate impairment in functioning [61].

Three studies examined the efficacy of the synthetic cannabinoid, nabilone, in treatment of PTSD symptoms. Jetly et al. [60] studied 10 participants with PTSD in a randomized, double-blinded, placebo-controlled clinical crossover trial. Exclusion criteria included significant cognitive impairment, serious medical conditions, or a positive screen for illicit substances. Participants were divided equally into two groups, receiving either nabilone or a placebo (unspecified), over a seven week period and the effects on PTSD-associated nightmares were observed. The treatment groups were then switched for another seven week period. Over each period, the initial dose of 0.5 mg was increased by 0.5 mg weekly to a maximum of 3.0 mg. One subject was unable to participate in the second period [60].

PTSD, Post-traumatic Stress Disorder; CBD, Cannabidiol; THC, Tetrahydrocannabinol.

Klumpers et al. [53] obtained similar results in their study, where 54 healthy volunteers were recruited for a randomized, double-blinded, placebo-controlled clinical trial and were given either synthetic Δ 9 -THC, d -cycloserine (DCS, a partial NMDA receptor agonist), or a placebo (unspecified). There were 31 females and 23 males aged 18–30, separated into 18 participants per group. Over the course of the study, two participants dropped out due to adverse effects of the THC, one was removed after testing positive for cannabis, and the EMG data of four participants was unusable due to equipment failure, bringing the study total down to 47 participants. Exclusion criteria included never having been exposed to marijuana, no current drug use, low startle reactivity, not pregnant, and no first or second-degree family members with a history of psychosis. Participants all underwent a form of fear conditioning on day 1, where participants were presented with two neutral faces, colored either blue or yellow. During the four fear conditioning trials, participants received a small shock on their wrist (CS+). The other four trials did not have an associated shock (CS−). On day 2, participants were given either 10.0 mg of Δ 9 -THC, 250.0 mg DCS or placebo. Extinction training commenced 2 h post-ingestion, consisting of two blocks of four CS+ and four CS− trials without shock reinforcement. Retention phases 1 and 2 occurred on day 4, which included two blocks without shock reinforcement. After the first retention phase, participants were also presented with a black screen and a fixation cross for 35 s and received three un-signaled shocks spaced 5 s apart to assess differential impact on retention between the substances. Startle response was measured with EMG from the orbicularis oculi muscle under the right eye, and SCR was measured by attaching two electrodes on the palm of the left hand [53].

The presented studies reveal promising evidence in favor of cannabinoids as a treatment option for individuals with PTSD. CBD and THC have been shown to be effective treatments for PTSD symptoms overall, as well as enhancing consolidation of extinction training used to eliminate conditioned fear. Nabilone, a synthetic cannabinoid developed for medicinal purposes, has shown to provide the same benefits as the cannabis extracts but with fewer adverse effects. By treating the fear memories and aiding with their extinction, it can be possible to treat the PTSD symptoms at the source of the cause.

Nabilone.

The results showed improvement in 70% of participants at the end of the nabilone treatment period, compared to 22.2% at the end of the placebo treatment period. Also, 44% at the end of the nabilone treatment period reported no distressing dreams during the last week. Efficacy was measured by the mean reduction in the CAPS Recurring and Distressing Scores, Frequency + Intensity, which showed to be significant (nabilone: −3.6 ± 2.4, mean ± SD, vs. placebo: −1.0 ± 2.1, p=0.03). Significant improvement was also observed in the nabilone groups in the Clinical Global Impression of Change (nabilone: 1.9 ± 1.1 vs. placebo: 3.2 ± 1.2, p=0.05) and the General Well Being Questionnaire reports (nabilone: increase from 28.4 ± 21.6 to 49.3 ± 21.6 vs. placebo: decrease from 29.0 ± 20.8 to 23.0 ± 17.2, p=0.04) [60].

Numerous treatment options have been developed for the disorder, including psychotherapeutic approaches such as exposure therapy, virtual reality therapy, cognitive behavioral therapies and eye movement desensitization and reprocessing. Around 40–70% of individuals receiving these treatments briefly have noticed significant improvement in symptoms and extinction of the learned fear [9]. Not all individuals are ideal candidates for these treatments, however. High rates of suicidality, dissociation, destructive impulsivity, and chaotic life problems are indications that the patients may not respond well to treatment, causing clinicians to become more likely to forgo attempting these therapies. This exposes a need for developing other therapy options [10].

PubMed was the primary database used to search for articles, with Google Scholar as a secondary database. The following keywords were used for the search: “nabilone”, “dronabinol”, “cannabidiol”, “cannabis”, “PTSD”, and “fear extinction”. Searches were then limited to human subjects, and studies within the last 10 years (2009–2019). This search yielded 148 articles, without any duplications. Figure 1 depicts how the articles were further discarded and chosen.

Using neuroimaging, different brain structures were observed to have hyperactivation or hypoactivation in response to PTSD symptoms. The amygdala has shown hyperresponsivity during these symptoms and a positive correlation linked with the degree of severity [38], and the medial prefrontal cortex has shown hyporesponsiveness during the symptoms and a negative correlation with severity [39], [ 40]. Hyperactivations of various brain structures, considered the “limbic” brain, have been observed in other anxiety disorders (e.g., social anxiety disorder and specific phobia disorder), but not hypoactivations. These hypoactivations observed during PTSD symptoms were in regions of the brain associated with the experience or regulation of emotions, further suggesting the involvement of impaired fear extinction [41]. Reduced 2-AG and AEA concentrations have also been observed in PTSD patients, giving more evidence of abnormal CB 1 receptor signaling [42], [ 43]. Administering synthetic cannabinoids to a healthy individual can cause an increased ventromedial prefrontal cortex and hippocampus activation to a conditioned stimulus previously extinguished during extinction memory recall, indicating its capacity to modulate prefrontal-limbic circuits during fear extinction and consolidation of the extinction memory [44], [ 45]. However, it is also important to recognize that long-term use of cannabinoids may limit its clinical efficacy, especially if the individual develops a tolerance to the treatment [46].

Fraser [15] tested nabilone for treatment-resistant nightmares in PTSD patients. This cohort study recruited 47 patients (27 females and 20 males) with an age range from 26 to 68. Inclusion criteria required the participants have a minimum current nightmare frequency of once weekly. They were initially given 0.5 mg of nabilone daily, which was increased or decreased to achieve optimal dose. The observed effective dose ranged from 0.2 to 4.0 mg. The patients were then seen weekly to monitor effects until either a satisfactory response was achieved, or treatment was terminated due to adverse effects (including light-headedness, forgetfulness, dizziness, and headaches). This study did not report any statistics or errors [15].

The studies chosen were based on one of three analysis methods: (1) Cohort studies of individuals diagnosed with PTSD who were administered a synthetic cannabinoid, (2) Case reports or series with similar methods described above for the cohort studies, or (3) Randomized, placebo-controlled, and double-blinded experimental clinical trials where the test subjects either currently had PTSD or were given a conditioned fear, generally in the form of an electric shock paired with a conditioned stimuli, before being administered the treatment. All reviews, systematic reviews and meta-analyses were excluded. The remaining 110 papers were analyzed for relevance, which greatly reduced the number of eligible papers. Exclusions included: (1) 22 papers that involved patients with PTSD and a co-morbid substance abuse disorder (usually cannabis), (2) 19 papers that examined how PTSD can increase cannabis use and vice versa, (3) four papers that investigated the effects of non-prescribed (uncontrolled) long-term cannabis use on PTSD symptoms, (4) three papers that looked at the changes experienced from cannabis on brain structures instead of PTSD symptoms or extinction training, (5) 28 papers where the primary focus was not on the PTSD experienced by the patients, and (6) 24 papers where the use of cannabinoids on PTSD symptoms and extinction training was not examined. These exclusions yielded 10 studies: four cohort studies, four randomized clinical trials, one case report, and one case series.

Before beginning the study, patients were given a tracking sheet to record hours of sleep and the intensity of their nightmares, with a scale from 1 to 5 (with five being the most intense). Throughout the study 34 patients experienced total cessation or a decrease in severity of nightmares, with 28 patients having total cessation of nightmares and six having satisfactory reduction. However, only four patients were able to successfully discontinue treatment following 4–12 months of the therapy without the nightmares returning. The other patients typically had reoccurrence of nightmares within the first two nights. Other benefits observed in some of the cases included improvement in sleep time, reduction of daytime flashbacks, and elimination of night sweats [15].

Cannabinoids have been shown to be an effective treatment option for patients with PTSD. Besides aiding to relieve the symptoms and enhance extinction training, they also are relatively well tolerated. Common adverse effects included light-headedness, forgetfulness, dizziness, and headaches.

The synthetic cannabinoids have been used as treatment for different diseases, including as an anti-emetic, for muscle spasms and pain associated with multiple sclerosis [29], for sleep disorders [30], pain and inflammation [31], and anxiolytic symptoms [32]. They have also been shown to alleviate cannabis withdrawal in users attempting to quit [33]. There are potential risks associated with the drugs, especially when they are abused, such as tachycardia, seizures, and hallucinations [34].

Post-traumatic Stress Disorder (PTSD) is a diagnosis of extreme anxiety caused by a traumatic event. Less than 10% of individuals who have experienced severe trauma will develop this disorder. Treatment options include various psychotherapies, but not all patients respond to them. Different pharmacological approaches have been explored as potential adjuvants, including using cannabinoids to target the endocannabinoid system to reduce the symptoms and enhance extinction training over the associated fear memories. This review was aimed to determine the effects of using cannabinoids for treatment of PTSD.

Cannabis extracts (THC or CBD)

Cannabis has been shown to have many clinical uses [16]. It is useful as an analgesic and anti-inflammatory, as well as in relieving associated depression, anxiety, and stress. The two major endogenous cannabinoids are N-arachinodoyl ethanolamine (anandamide, AEA), which acts as a partial agonist [17], and 2-arachidonoyl glycerol (2-AG), which acts as a full agonist [18], [ 19]. They bind to the two G-protein-coupled receptors that make up the endocannabinoid system, distributed throughout the brain. This system has been implicated in emotional learning and memory processing, both physiologically and pathologically [20]. The cannabinoid receptor type 1 (CB 1 receptor) is involved in modulating various neuronal activities, such as synaptic transmission, while the cannabinoid receptor type 2 (CB 2 receptor) is mostly involved with immune response [21], [ 22].

Δ 9 -tetrahydrocannabinol (THC) is the principal psychoactive component of cannabis. It acts as a partial agonist at both the CB 1 and CB 2 receptors, most likely exerting its psychoactive effects through the former [23]. These effects include relaxation, elevated mood, paranoia, perceptual alterations, and cognitive deficits [24]. Stress relief is the primary reason chronic use occurs in cannabis users, regardless of the other adverse effects [25]. Cannabidiol (CBD) can also be extracted from cannabis; however, it does not produce the same psychoactive effects as THC. CBD also interacts with the CB receptors, but there is growing evidence that suggests it exerts many of its effects via interaction with the 5HT 1A receptor [26].

Elms et al. [58] is a retrospective case series that examined the effect of oral CBD on the symptoms of PTSD in 11 adult patients who were receiving treatment at an outpatient psychiatric clinic. Inclusion criteria for the series included a cut-off score of 33 on the PTSD Checklist for the DSM-5 (PCL-5) and at minimum two follow-up appointments after the initial appointment, decreasing the original 21 patients down to these 11. Presence of another psychiatric comorbidity, aside from an active thought disorder, did not exclude the patient from the study. Four of the patients received CBD as an oral capsule (22.0–28.0 mg), one received it in an oral liquid spray (about 1.5 mg), and six received both forms either concurrently or sequentially throughout the study. They were instructed to take CBD once or twice a day, depending on severity of symptoms, which equated to a median oral capsular dose of 25.0 mg and a median liquid dose of 9.0 mg per day. The dose was adjusted at each four week appointment based on effectiveness. The mean total dose of CBD at the conclusion of the study period at eight weeks was 48.64 mg. The PCL-5 assessment was completed by the patients every four weeks to monitor for changes to their PTSD symptoms. Side effects and tolerability were assessed and analyzed through patient self-reporting, as well as any comments or complaints [58].

Similar weaknesses are also found in Elms et al. [58], where not only is the sample size small but the patients were also being treated for other psychiatric comorbidities when initiating the CBD treatments. These other medications included antidepressants, anticonvulsants, antipsychotics, anxiolytics, and beta-blockers. Some patients also used cannabis daily, although were not considered to have an SUD. As in the Shannon [55] case report, it is impossible to determine whether these therapies influenced the effect of the CBD, which casts doubt on the overall findings. The method for receiving the CBD varied among the patients as well, without a precise dosing system. Without a definitive guideline for administration, it limits the ability to determine what amount of CBD produces optimal effects on PTSD symptoms.

For this review, four cohort studies, four randomized clinical trials, one case report, and one case series were obtained from PubMed within the last 10 years. Cannabis extracts, tetrahydrocannabinol (THC) and cannabidiol (CBD), and synthetic cannabinoids were used in the studies to target the cannabinoid receptors 1 and 2. Cannabinoids were shown to improve overall PTSD symptoms, including sleep quality and quantity, hyperarousal, and treatment-resistant nightmares. When participants were undergoing extinction training, cannabinoids given within the same time interval enhanced consolidation and retention.

A significant characteristic of PTSD is an elevated fear response in relation to the traumatic event. Regulation of emotions through fear extinction has been determined to be impaired in the disorder, which leads to the prolonged symptoms. This impairment is acquired due to the traumatic event, as opposed to developing from a predisposing factor. Individuals also have been observed to have an attention bias toward the stimuli, which increases the expression of fear [7], [ 8].

There was no difference between the two groups in terms of fear acquisition, or early extinction learning, but those in the THC group exhibited a lower increase in SCR score when exposed to the stimulus during extinction recall (late extinction learning 0.13 ± 0.05, mean ± SEM, vs. extinction recall test 0.22 ± 0.08) in comparison to the placebo group (late extinction learning 0.13 ± 0.04 vs. extinction recall test 0.37 ± 0.11). While there was no significant increase observed in the THC group (p=0.37), there was a significant difference in the placebo group (p<0.05), indicating THC had likely helped keep the extinguished fear from returning upon re-exposure to the stimuli [52].

Figure 1:

Results for recall indicated a main effect of group ( F [2, 40]=2.991, p=0.062, η p 2 =0.13), which aligns with the lower post correction ratings observed when CBD was administered post-extinction (p=0.047). This indicates a consolidation of extinction learning. However, no difference was observed between CBD pre-extinction and placebo administrations. Significantly greater SCRs to the CS+ than the CS− in conditioning context were also observed, indicating a higher shock expectancy ( t [37]=2.796, p=0.008). SCRs also exhibited a trend in the reinstatement phase for a group and context interaction ( F [2, 35]=2.836, p=0.073, η p 2 =0.147), reflecting how CBD administered either pre- or post-extinction resulted in a trend level of reduction in reinstatement of autonomic contextual responding (p=0.045); however, this effect did not reach significance post-correction [54].

A significant decrease (p<0.0001) in CAPS scores was observed from before and after cannabis use, from 98.8 ± 17.6 (mean ± SD) to 22.5 ± 16.9, indicating a reduction in overall PTSD symptoms. Even when CAPS scores were examined for individual Criteria groups (B: re-experiencing, C: numbing and avoidance, D: hyperarousal), a significant reduction was observed (p<0.0001) in each. Criterion B decreased from 29.5 ± 6.4 to 7.3 ± 5.9, Criterion C from 38.2 ± 8.4 to 8.7 ± 8.0, and Criterion D, from 31.0 ± 6.2 to 6.6 ± 6.0. Criterion A relates to the presence of traumatic events and immediate emotional response to them, and thus a change in score could not be obtained [51].

Post-traumatic stress disorder (PTSD) first became recognized as a diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III). An individual with this diagnosis has experienced a traumatic event that invoked extreme emotions, including severe anxiety. Previously, PTSD rates were typically studied in individuals exposed to specific traumatic events (e.g., combat, assault, rape, etc.), but newer studies have since moved to assessing the general population for PTSD [1], [ 2]. Diagnosis for PTSD must also account for survivors with prolonged, repeat trauma, which has a more complex psychological impact on the individual [3]. The criteria for PTSD have evolved across the DSM editions, with the most recent fifth edition addressing several ambiguities and errors from the previous editions. These include validity of the diagnosis, the trauma symptoms, the role of symptoms in defining its psychopathology, differentiation from other disorders, and various specifiers [4]. However, exposure to a traumatic event does not automatically cause PTSD in an individual. On average, less than 10% of individuals exposed to a traumatic event will develop the disorder, and 6.8% will experience it lifelong [5], [ 6].

In the next study, Rabinak et al. [52] conducted a randomized, double-blinded, placebo-controlled clinical trial. The study recruited 29 healthy volunteers, 12 males and 17 females aged 21–45. Thirteen participants had a minimal history of marijuana use as defined by the authors, while none had a history of neurological, psychiatric or medical illness. The females also participated in the study when their estrogen levels were low. On day 1 of the study, subjects underwent partial discrimination fear conditioning involving two neutral visual stimuli and bursts of noise. Participants were presented with one of the two stimuli on a computer screen, followed by an aversive white noise burst through headphones (CS + U). The conditioning consisted of 15 non-reinforced presentations of the stimuli mixed with eight presentations of the stimuli followed by noise. A third stimuli was also presented, but never paired with the noise (CS−). Skin conductance response (SCR) was measured by attaching carbon fiber electrodes between the first and second phalanges of the second and third digits of the left hand. It was during the subsequent extinction training on day 2 where the conditioned response to one of the stimuli was extinguished (CS + E). Then, the participants were randomly assigned to receive a capsule with 7.5 mg of THC (the lowest effective dose that produces behavioral and subjective effects) or a placebo capsule containing only dextrose. The extinction training involved 15 presentations of CS + E and 15 presentations of CS−. Day 3 assessed extinction retention through 20 non-reinforced presentation of all the stimuli (CS + E, CS + U, and CS−), and during presentation of each stimuli the participants indicated whether they would hear an associated noise burst [52].

Two synthetic cannabinoids have been developed for medical uses, both producing similar effects to oral administration of natural cannabis but without the psychoactive properties [27]. Nabilone is a synthetic cannabinoid administered orally and is most similar chemically to Δ 9 -tetrahydrocannabinol (Δ 9 -THC). It is generally prescribed for nausea and vomiting associated with chemotherapy in patients resistant to conventional antiemetic treatments. Dronabinol is another synthetic cannabinoid, also prescribed for nausea and vomiting associated with chemotherapy, as well as anorexia associated with weight loss in patients with Acquired Immune Deficiency Syndrome (AIDS) [28].

Numerous studies have used the rat model to test the effects of cannabinoids on extinction training. CB 1 receptors in the brain were initially examined in the rat model where antagonization produced an observed impairment of fear extinction retention to a conditioned fear. It was suggested CB 1 receptor activation does not supress fear but rather helps to extinguish it and is not involved in its initial acquisition [37], [ 47]. Genetic variability in the CB 1 receptor has also been shown to play a role in effective fear extinction. The difference in the alleles dictates how robust the observed extinction of fear will be, perhaps helping to explain the underlying differences in anxiety throughout the population [48]. Repeated injection of CBD into the infralimbic cortex has been shown to facilitate fear extinction and prevent reconsolidation of the contextual fear [49]. Using drugs to increase endocannabinoid neurotransmission could prove an effective tool in combination with exposure therapies in treatment of PTSD [50].

While Shannon [55] reported similar results observed in the previous studies, case reports come with their own weaknesses. For instance, there is only one participant being followed. This creates a significant sampling size bias. This limits the validity of the results as they have not been reproduced more than once. The patient in this study was also on other supplements when she started the CBD treatments. There is no way to tell if any of the other medications altered the effects of the CBD, which then brings the validity of the results into question. While the child appeared to greatly benefit from the CBD, she would need to be followed for longer while only taking the CBD treatment to fully understand its effects and benefits.

Three years after the initial evaluation, the patient was started on a trial of CBD oil. CBD supplements of 25.0 mg were given at bedtime, and 6.0–12.0 mg of CBD sublingual spray was administered during the day as needed for anxiety. Gradually over five months the patient experienced an increase in sleep, both in quality and quantity, and a decrease in anxiety. This was measured by administering the Sleep Disturbance Scale for Children and the Screen for Anxiety Related Disorders (SCARED) over the five months, where each score was observed to fall for the patient. A score of more than 50 on the Sleep scale is indicative of a sleep disorder, and a SCARED score over 25 is indicative of a highly probable anxiety disorder [56], [ 57]. The patient experienced a Sleep scale score decrease from 59 to 38, and a SCARED score decrease from 34 to 18 [55].

"CBD was given on an open-label, flexible dosing regimen to patients diagnosed with PTSD by a mental health professional."

And now research suggests it could chase away night horrors too.

"We have lots of customers who say they take CBD Armour to get a better night's sleep and generally feel more relaxed when they do. "If CBD oil can contribute to staving off PTSD and nightmares then here's to a better nights sleep all round. “And other studies have shown how cannabidiol can improve symptoms of anxiety while also promoting better sleep.”

The Endocannabinoid System is a complex network of cannabinoid receptors found in both the central and periperhal nervous system. While ECS is active in everyone, in some cases it’s not functioning perfectly, which results in hormone imbalances and the exacerbation of fears.

"CBD has seen a recent surge in research regarding its potential value in a number of neuropsychiatric conditions," adds Lucas. A total of 11 participants took part in his study over an eight-week period.

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"CBD also appeared to offer relief in a subset of patients who reported frequent nightmares as a symptom of their PTSD." CBD oil specialist and UK supplier David Barcly, founder of CBD Armour, says he's not surprised by the findings as he claims CBD oil has helped people deal with stress and anxiety, and led to better sleep quality overall.

Post-traumatic stress disorder is an anxiety disorder caused by a distressing, frightening or extremely stressful event. According to the NHS website, someone with PTSD often relives the traumatic event through nightmares and flashbacks.

"This effect is believed to be due to the action of CBD on the endocannabinoid system (ECS)," says Lucas who conducted the study at Rocky Vista University in Parker, Colorado, USA.

"CBD appeared to offer relief in a subset of patients who reported frequent nightmares as a symptom of their PTSD," says study lead author Lucas Elms.

"CBD was generally well tolerated and no patients discontinued treatment due to side effects. "Administration of oral CBD in addition to routine psychiatric care was associated with PTSD symptom reduction.

"CBD appears to be better tolerated that routine psychiatric medications," says Dr Scott Shannon, sleep and anxiety study author.

A recent study to determine whether CBD helps improve sleep and/or anxiety was conducted at the University of Colorado's Department of Psychiatry in Denver. Within the first month 57 patients out of 72 noticed decreased anxiety after taking CBD and sleep quality improved with the same time period for 48 of the subjects.

People who suffer from harrowing nightmares and a fear of things that go bump in the night are turning to cannabis oil as an alternative treatment. A new study claims it could help prevent traumatic dreams, especially for those who suffer some form of Post Traumatic Stress Disorder (PTSD).

Lucas adds that patients also received routine psychiatric care which included medication and psychotherapy.

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"Furthermore, CBD displays promise as a tool for reducing anxiety in clinical populations." ​Cannabidiol is entirely legal in the UK and sold as a food supplement as well as in skin and hair products. It's extracted from cannabis plants but contains only trace amounts if the high-giving tetrahydrocannabinol (THC) chemical.

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