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Cannabinoids in SCI

Risks and Side Effects

Side effects common in the SCI population using cannabis include dry mouth, fatigue, and hunger (Nabata et al. 2020). Most short-term side effects are mild to moderate and dose-dependent (NAS 2017). Naïve users of cannabis may experience acute overdose symptoms including feelings of anxiety and panic, combined with nausea, vomiting, and possibly fainting as well as symptoms of misperception and distortion of time and space (Hagenbach et al. 2007; Wilsey et al. 2008; Office of Medical Cannabis of the Netherlands 2019). Studies show that autonomic, cardiovascular, and respiratory side effects are not common in SCI patients using cannabis, but more research is needed (Nabata et al. 2020; Hagenbach et al. 2007; NAS 2017). Cannabis use may lead to depressive and anxious symptoms, though these are not commonly reported by SCI patients in studies. Long term use of cannabis is associated with tolerance, dependence, and withdrawal symptoms when long-term use is ceased (Hall & Degenhardt (H&D) 2009; NAS 2017). Some individuals develop cannabis dependence syndrome; life-time risk is 9% for cannabis users in general. Long term use of cannabis is associated with chronic psychotic illness, usually before the age of 26, though causality is unclear (H&D 2009; Arsenault et al. 2002). There is a need for more high-quality research studies with a rigorous design, that are longer-term, and follow a double-blinded, randomized controlled trial design.

Risks and side effects associated with therapeutic and recreational use of cannabis in the general population has been studied more than in those with spinal cord injury. Many short-term side effects were dose-dependent and were reported as mild to moderately severe (NAS, 2017). These included red, dry eyes that feel heavy, altered skin sensations of cold/heat and increased hunger (H&D 2009). A few studies report on side effects as secondary outcomes in SCI studies and showed that dry mouth, fatigue and hunger are the most common side effects, and they tend to be experienced as mild. Moderate side effects reported included constipation, fatigue and abdominal discomfort, no severe side effects were reported (Nabata et al. 2020). In the general population the most common short-term physical side effects include dry mouth, muscle weakness, headache, light-headedness, dizziness, irritation of airways and tachycardia (NAS 2017; H&D 2009). There is a weak association between cannabis use and psychosis, and other studies show no increased psychosis incidence (H&D 2009). However, other studies show that a baseline history of cannabis use increases the risk of a follow-up psychosis outcome for patients with no previous psychosis outcomes. Long-term effects of cannabis on risk of psychosis outcome may be due to dysregulation of endogenous cannabinoid systems (van Os et al. 2002). The risks associated with smoking cannabis are like smoking tobacco (Health Canada 2018). All routes of administration, such as orally, rectally, and parenterally, are free of the risk of chronic inflammatory disease and upper respiratory cancer.

Autonomic Functions

Few autonomic side effects with cannabis use have been reported for people with SCI (Nabata et al. 2020) but given the typical prevalence of autonomic dysfunction in spinal cord injury, these functions should be closely monitored. Wade et al. (2003) showed no effect on incontinence frequency or severity, bladder urgency, or nocturia per night. No reported impact on ECG in two studies (Hagenbach et al. 2007; Wilsey et al. 2016). Following a 6-week intervention of dronabinol, blood pressure significantly decreased in the intervention group, in comparison to increased blood pressure among people in the placebo group (Hagenbach et al. 2007). Decreased blood pressure may be a risk for a side event (e.g., fall), for those with postural hypotension. Prolonged use of cannabis administered by inhalation has been associated with increased risk of chronic obstructive pulmonary disease (COPD), chronic bronchitis, and recurring respiratory infections (NAS 2017). Prolonged cannabis use has also been associated with a slightly increased chance of triggering a myocardial infarction in high risk individuals (NAS 2017), as well as with increased mortality rates after myocardial infarction in frequent cannabis users in comparison to myocardial infarction patients who were not frequent users of cannabis (H&D 2009). A recently published case report identifies that cannabis use improved blood pressure stability by reducing intensity and frequency to the visceral stimuli (Nightingale et al. 2020).

Cognition

Cannabis and THC produce dose-related impairments in reaction time, information processing, perceptual–motor coordination, motor performance, attention, and tracking behaviour (NAS 2017; H&D 2009). Moreover, cannabis lingers in the body long after use, particularly in fatty tissues like the brain, meaning task performance may be impaired long after the psychoactive effects wear off. Experimental studies with SCI show mixed results on cognition with side effects like a decrease in objective concentration, memory, learning and psychomotor speed reported by participants taking THC rich products (Wilsey et al. 2008; Wade et al. 2003), whereas other studies show no side effects on cognition in people with SCI when using THC rich products or THC/CBD mixed products (Kogel et al. 1995; Hagenbach et al. 2007; Wade et al. 2003). It is recommended to avoid operating heavy machinery or performing dangerous activities for 3 hours after inhaling cannabis, 6 hours after oral ingestion of cannabis, and 8 hours if a “high” is experienced (Kahan et al. 2014). Driving laws in Canada state that driving after using cannabis is a punishable offence. Cannabis tests are positive when a blood serum value of 2 ng/ml or more two hours after driving is registered (Brubacher et al. 2019; by comparison, one inhalation of 100 mg of standardized 9.4% THC cannabis will raise serum levels to 45 ng/ml) and combined with the unpredictable half-life time of THC and its metabolites, it is hard to estimate when driving is safe and legal after using cannabinoids. It is therefore advisable to never mix cannabis use and driving. Examples of high-risk activities with regards to SCI may include performing transfers, operating heavy machinery, and participating in physical therapy sessions. Cannabis-induced cognitive impairment has been shown to be reversible within 2-3 months when cannabis use is stopped (NAS 2017).

Mental Health and Wellness

In the non-SCI population, long term use has been associated with physical dependence and withdrawal; this causes a range of symptoms, most notably anxiety, restlessness, irritability, insomnia, and nausea. Cannabis use is also associated with an increased chance of mood and anxiety disorders, as well as decreased motivation. Two experimental studies in SCI showed no effects of cannabis on mood and emotion (Hagenbach et al. 2007; Wilsey et al. 2008) and one study showed a decrease of vigor and an increase in at least one dysphoric mood state (anger, tension) in participants taking dronabinol (Kogel et al. 1995). Acute intoxication by taking a high dose of THC in a short amount of time can cause feelings of anxiety and panic, combined with nausea, vomiting and possibly fainting as well as symptoms of misperception and distortion of time and space; briefly altering how one perceives and experiences the world (Office of Medical Cannabis of the Netherlands 2019). These negative effects are most often reported by new users (naïve cannabis users) and are considered an acute overdose in relative terms; physically overdosing on cannabis requires immense amounts being ingested in a short period of time (NAS 2017).

Long term cannabis use has been associated with chronic psychotic disorders, most notably schizophrenia. It is still unclear if cannabis use causes schizophrenia, triggers schizophrenia in at-risk individuals, or if individuals who already have schizophrenia use cannabis to self-medicate (NAS 2017). An emerging concern is the potentially greater side effects that cannabis use may have on adolescents and young adults. Cannabis use early in adolescence may alter brain development and could be related to the development of psychotic disorders as adults (H&D 2009; NAS 2017). Long-term use can also lead to cannabis dependence syndrome, which consists of a combination of tolerance to effects, impaired control over use, psychological and cognitive side effects and a failure to cease usage despite its harmful effects (H&D 2009; NAS 2017). Lifetime risk for cannabis users developing cannabis dependence syndrome is 9% (H&D 2009). This risk increases when age of initiation is earlier, with dose, and with frequency of use (NAS 2017).

Illegal synthetic cannabinoids are made to imitate the psychoactive effects of THC but are made of different substances; this makes their effects on the body highly unpredictable (National Center for Environmental Health 2018). Illegal synthetic cannabinoids compounds like “K2” and “Spice” are often combined with plant-based cannabis products or mixed with other dangerous and often addictive substances and have been responsible for serious side-effects and overdoses (Canadian Centre on Substance Abuse 2014). Production, distribution, and use associated with non-prescription synthetic cannabinoids are illegal in Canada (Health Canada 2013). Besides their varying concentrations, their capacity to bind with the cannabinoid receptors of the body is usually much stronger, increasing risk of overdose.

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