Post-Traumatic Stress Disorder

Recent preclinical research has found that cannabis can help suppress traumatic memories or flashbacks, as well as improving sleep, anxiety, avoidance and hyperactivity symptoms related to PTSD. (Backes, 2017) This shows significant potential for cannabinoid therapies in relation to PTSD.

A 2017 review (Lee et al, 2017) of studies related to cannabis and fear memories found evidence that supports CBD’s potential as treatment for lingering traumatic memories and their impacts. Oral THC has also been found effective in improving sleep duration and quality, and reducing nightmares and daytime flashbacks among treatment-resistant PTSD patients (Roitman et al, 2014).

The endocannabinoid system’s signaling mechanisms are key to the body’s adaptation to stress and recovery after a stressful event (Backes, 2017). We know that CB1 receptors are concentrated in the anatomic areas of the “fear network” (Backes, 2017) – the amygdala, hippocampus, and ventromedial prefrontal cortex. Changes in endocannabinoid signaling, lowering of anandamide levels and abnormal CB1 receptor densities are common in PTSD patients (Loflin et al, 2017).

Epidemiological studies report positive finding in the use of cannabis to alleviate symptoms of PTSD (Couge et al, 2011). Cross-sectional studies indicate patients reported using it to cope with hyperarousal, coping, sleep (Bremner et al, 1996). One study found reductions of 75% in symptoms of trauma-related re-experiencing, avoidance and hyperarousal (Greer et al, 2014).

Overall, current evidence indicates CBD has considerable potential as a treatment for multiple anxiety disorders (SAD, GAD, Panic Disorder), with need for further study of chronic and therapeutic effects in relevant clinical populations. Evidence from a small number of clinical studies of prescription cannabinoids containing small amounts of THC suggests that these drugs could improve symptoms of anxiety and depression in patients suffering from anxiety and/or depression secondary to certain chronic diseases (e.g. patients with HIV/AIDS, MS, and chronic neuropathic pain) (Blessing et al, 2015)

Unknown or expected adverse effects, risks and safety issues & related toxicology:

A systematic review by Whiting et al. (2015) stated in their conclusions that “Cannabinoids were associated with an increased risk of short-term adverse effects”.

According to the Guidance for the Use of Medicinal Cannabis in Australia: Overview, Therapeutics Good Administration

(2017): Cannabis is not appropriate for patients who:

• Are under the age of 25 (with the exception of intractable epilepsy or severe pain syndrome)
• Have a personal history or strong family history of psychosis
• Have a current or past cannabis use disorder, or active substance use disorder
• Have unstable respiratory or cardiovascular disease (including angina, peripheral vascular disease, cerebrovascular disease, arrhythmias)
• Are pregnant, planning to become pregnant, or

Breastfeeding.

Cannabis should be authorized with caution in patients who:

• Smoke tobacco
• Have risk factors for cardiovascular disease
• Are heavy users of alcohol
• Are taking sedating medications or any other medication metabolized by the CYP450 pathway
• At risk or have liver disease

Potential drug interactions

Increasing THC concentration:

Examples of inhibitors:

– Antidepressants (e.g. Fluoxetine, Fluvoxamine)

– Proton Pump Inhibitors (e.g. Omeprazole)

– Cimetidine

– Macrolides (Clarithromycin, Erythromycin)

– Antimycotics (e.g. Itraconazole, Fluconazole, Ketoconazole, Miconazole)

– Calcium Antagonists (e.g. Diltiazem, Verapamil)

– HIV protease inhibitors (e.g. Ritonavir)

– Amiodarone

– Isoniazid

– Grapefruit juice

Increasing CBD concentration:

– Metabolized by CYP 2C19 and CYP 3A4

– Bioavailability could be increased by many of the same substances as for THC

Decreasing THC and CBD concentration:

• CYP 2C9 and 3A4 Inducers accelerate THC and CBD metabolism
• Examples of inducers:

– Rifampicin

– Primidone

– Carbamazepine

– Phenobarbital

– Phenytoin

– Rifabutin

– Saint John’s Wort

Significantly changed serum levels of clobazam, rufinamide, topiramate, zonisamide, and eslicarbazepine were seen in the study by Gaston et al (2017) on interactions between cannabidiol (Epidiolex.) and commonly used antiepileptic

drugs. Abnormal liver function test results were noted in participants taking concomitant valproate. This study emphasizes the importance of monitoring serum AED levels and LFTs during treatment with supraphysiological doses of CBD (e.g. 1000mg/kg).

• Caution with blood thinners like Warfarin, Heparin,

Clopidogrel (Plavix)

• Additionally, pharmacodynamic interactions should be expected between cannabis and drugs with sympathomimetic activity (tachycardia,

hypertension), central nervous system depressants (drowsiness, ataxia), and drugs with anticholinergic effects (tachycardia, drowsiness).

Many of these drug interactions can be mitigated in complex patients with polypharmacy by slowly titrating cannabis.