Sleep Disorders

Sleep is an essential and vital restorative process. Sleeping disorders are increasingly common and frequent in society, being known that when untreated, they can have repercussions through various pathological conditions such as cardiovascular diseases, anxiety, depression, metabolic and cognitive dysfunctions.¹

The potential of cannabinoid compounds in sleep disorders therapy has aroused investigations, in which evidence has been gathered indicating the role of cannabis in conditions such as insomnia, difficulty initiating and maintaining sleep, poor sleep quality, daytime sleepiness , recurrence of nightmares and sleep issues related to post-traumatic stress.

In fact, several studies show that cannabis can be valuable for sleep disorders, by promoting more easily and quickly the induction of sleep, reducing the occurrence of premature awakenings, increasing low-wave frequency sleep and reducing REM sleep. However, what is known is that such positive effects seem to be more related to the acute use of cannabinoid compounds, so that the long-term effects of this therapy should be better understood.¹

Cannabinoid compounds can bring benefits to cases of sleep disorders not only by acting on sleep’s intrinsic processes, but also by their activity in pain control. It is common for fibromyalgic patients, for example, to experience difficulties in sleeping, for the simple fact that their chronic pain does not allow the necessary relaxation for them to fall asleep.² Evidences shows that the ingestion of phytocannabinoids can produce analgesic, anxiolytic, antispasmodic, muscle relaxant, anti-inflammatory and anticonvulsant effects in the human body.³ Such benefits can bring comfort to many patients who suffer from chronic conditions, helping them with their sleeping processes.

A study conducted on a group of healthy patients suffering from insomnia evaluated the hypnotic activity of isolated THC delta 9. The study lasted 6 weeks and involved the administration of doses of 10, 20 and 30mg of THC and a placebo substance. The potential for THC to facilitate the process of sleep initiation was evidenced in all the doses studied, but the dosage of 20mg was the one that most induced participants to go to bed earlier and to sleep faster. On average, patients who received the 20mg dosage fell asleep 62 minutes earlier than those in the placebo group. Also, in a dose-dependent manner, a reduction in the number and duration of nocturnal awakenings was observed within the first 4 hours after falling asleep in the studied participants.4

It appears that the sleep-promoting activity of THC may suffer with pharmacological tolerance, and it may be necessary to increase the dosage of cannabis extracts over time to ensure the maintenance of such beneficial sleep effects.5

Another study analyzed the evolution of patients who started therapy with medical cannabis as a way of replacing regularly used drugs for pain, anxiety and sleep disorders. This study was developed through an electronic questionnaire, counting with 1513 participants. The results show that among patients who used medications for sleep disorders, 65.2% were able to reduce their medications when they introduced cannabis as a therapeutic alternative. Also, of those who regularly used opioid substances, 76.7% were able to reduce it. This reduction pattern corresponded to 71.8% for patients using anxiolytics, 66.7% for patients using migraine medications, 42% for those using alcoholic substances, and 37.6% for patients using antidepressants, as shown in the following chart.6

Fig 1. Percentage of patients who, with cannabinoid therapy, could reduce the use of: opioids for pain, anxiolytics, medications for migraine and sleep disorders, alcohol and antidepressants – in orange, the percentage of patients who achieved a slight reduction and, in green, patients who achieved a strong reduction.

Considering sleep disorders, CBD appears to have a dual activity. While some studies raise its benefits in providing sleep, others show its relevance in the symptoms of narcolepsy, in which CBD would be a good ally to help with the excessive daytime sleepiness resulting from this condition. That is due to CBD’s ability to increase alertness and reduce REM and non-REM sleep during the day, under the effect of light. This is associated with the activation of lateral hypothalamic neurons and the dorsal raphe nucleus, in addition to an increase in dopaminergic concentration related to the use of CBD.7 Such duality of CBD may be interesting as it is dependent on luminosity, which may benefit the patient in sleeping during the night and in maintaining alertness during the day.

Medical cannabis also has a promising therapeutic role in Post Traumatic Stress Disorder (PTSD), which is often accompanied by insomnia and frequent nightmares. This syndrome affects about 10% of the population, at some point in life, and has few effective pharmacological alternatives. Here, cannabinoid compounds may be beneficial with their anxiolytic activity, in addition to reducing the state of hypervigilance and nighttime awakenings, through their potential action on the limbic and paralimbic systems. The literature also indicates the role of CBD in the processing of traumatic memories, proving to be important in the negative modulation of their consolidation and revival and in the positive modulation of the deletion of such harmful memories, related to post-traumatic stress and its consequences on sleep.8 This same modulation of traumatic memories is essential to bring relief from nightmares, which can be very recurrent in the context of PTSD. In fact, the reduction in the frequency of nightmares and negative flashbacks has already been evidenced in some studies conducted with individuals with PTSD treated with cannabinoid derivatives.9,10

Overall, it can be said that medical cannabis can be very promising in the therapy of sleep disorders, but it is important to note that, as evidenced by the literature, such therapy will depend fundamentally on the cannabinoid compound, or in the association of cannabinoid compounds involved, on the dosage used and on the duration of the therapy.

References:

  1. WALSH, J. H.; EASTWOOD, P. R. Cannabinoids for sleep disorders: Weeding through the evidence. Sleep Medicine Reviews, v. 53, p. 101363, out. 2020.
  2. WARE, M. A. et al. The Effects of Nabilone on Sleep in Fibromyalgia: Results of a Randomized Controlled Trial. Anesthesia & Analgesia, v. 110, n. 2, p. 604–610, fev. 2010.
  3. ANDRE, C. M.; HAUSMAN, J.-F.; GUERRIERO, G. Cannabis sativa: The Plant of the Thousand and One Molecules. Frontiers in Plant Science, v. 7, 4 fev. 2016.
  4. COUSENS, K.; DIMASCIO, A. (?)?9 THC as an hypnotic. Psychopharmacologia, v. 33, n. 4, p. 355–364, 1973.
  5. KESNER, A. J.; LOVINGER, D. M. Cannabinoids, Endocannabinoids and Sleep. Frontiers in Molecular Neuroscience, v. 13, 22 jul. 2020.
  6. PIPER, B. J. et al. Substitution of medical cannabis for pharmaceutical agents for pain, anxiety, and sleep. Journal of Psychopharmacology, v. 31, n. 5, p. 569–575, 4 abr. 2017.
  7. KAUL, M.; ZEE, P. C.; SAHNI, A. S. Effects of Cannabinoids on Sleep and their Therapeutic Potential for Sleep Disorders. Neurotherapeutics, 12 fev. 2021.
  8. BITENCOURT, R. M.; TAKAHASHI, R. N. Cannabidiol as a Therapeutic Alternative for Post-traumatic Stress Disorder: From Bench Research to Confirmation in Human Trials. Frontiers in Neuroscience, v. 12, 24 jul. 2018.
  9. JETLY, R. et al. The efficacy of nabilone, a synthetic cannabinoid, in the treatment of PTSD-associated nightmares: A preliminary randomized, double-blind, placebo-controlled cross-over design study. Psychoneuroendocrinology, v. 51, p. 585–588, jan. 2015.
  10. FRASER, G. A. The use of a synthetic cannabinoid in the management of treatment-resistant nightmares in posttraumatic stress disorder (PTSD). CNS neuroscience & therapeutics, v. 15, n. 1, p. 84–8, 2009.