Sativex® (nabiximols) is an oromucosal cannabinoid drug that contains 2.7 mg THC and 2.5 mg CBD per spray. It has been approved by regulators in 29 countries for the treatment of spasticity in multiple sclerosis.
The medical application of cannabis began very early. From the mid-19th century to the 20th century, it was used by the mainstream in Europe and North America. Later, because people believed that its composition was unclear, quality control was difficult, and there were problems with abuse, it began to be gradually regulated and even banned. Since then, cannabis has become a plant that people are afraid of and stay away from. But now, we have to admit that cannabis has very important medicinal value.
THC is the main psychoactive component of cannabis, acting primarily as a weak agonist at CB1 and CB2 receptors, mediating pain, appetite, digestion, mood, and thought processes through the endocannabinoid system, a homeostatic regulator of multiple physiological functions found in all chordates. THC can cause psychiatric adverse events, depending on the dose and the patient's previous tolerance. Its use is indicated for many symptoms and conditions, including; pain, nausea, spasticity, appetite stimulation, anxiety, depression, post-traumatic stress disorder (PTSD), insomnia, and more. In contrast, CBD has little direct affinity for these receptors, but is a negative allosteric modulator of the CB1 receptor, with multiple effects such as analgesia, anti-inflammatory, anxiolytic, and antipsychotic. CBD is non-addictive and has been shown to help treat similar symptoms, with the added benefit of being an anticonvulsant, antipsychotic, neuroprotectant, and anti-inflammatory (including for autoimmune diseases). Cannabis is a multimodal treatment approach. It can be used to treat multiple symptoms and conditions simultaneously, thus helping to reduce the burden of multiple medications.
Cannabis can be a useful tool for treating many complex or rare conditions, such as:
There is strong, conclusive, or substantial evidence that cannabis can be used for:
• Chronic pain in adults
• Spasticity symptoms in multiple sclerosis
• Treatment of chemotherapy-induced nausea and vomiting
• Refractory seizures and Dravet syndrome
• Lennox-Gastaut syndrome (CBD)
Moderate evidence that cannabis can be used for:
• Improving outcomes in patients with sleep disorders associated with chronic pain, multiple sclerosis, fibromyalgia, and obstructive sleep apnea syndrome
• Reducing intraocular pressure in patients with glaucoma
Limited evidence that cannabis can be used for:
• Symptoms of dementia
• Symptoms of Parkinson's disease
• Positive and negative symptoms of schizophrenia
• Symptoms of post-traumatic stress disorder
• Appetite and weight loss associated with HIV/AIDS
• Spasticity in multiple sclerosis (clinician-measured) Disability, mortality, and other outcomes associated with traumatic brain injury/intracranial hemorrhage
• Anxiety symptoms in social anxiety disorder (CBD)
• Symptoms of Tourette syndrome
Smoking
• Most common route of administration, but not recommended (joints, bongs, pipes, etc.)
• Combustion at 600–900 °C producing toxic biproducts: tar, PAH (polycyclic aromatic hydrocarbons), carbon monoxide (CO), ammonia (NH3).
• Chronic use associated with respiratory symptoms (bronchitis, cough, phlegm), but not lung cancer nor COPD (if cannabis only).
• Patients may mix with tobacco increasing respiratory/cancer risk
• 30–50% of cannabis is lost to ‘side-stream’ smoke
Vaporisation
• Heats cannabis at 160–230 °C. Reduced CO, but not complete elimination of PAH demonstrated to date.
• Vaporisation produces significantly less harmful biproducts vs. smoking.
• Decreased pulmonary symptoms reported compared to smoking.
Oral
• Oils, capsules and other po routes increasingly popular due to convenience and accuracy of dosing.
• Edibles (brownies/cookies) may be more difficult to dose.
• Juicing and cannabis teas do not allow for adequate decarboxylation of raw plant
• Nabiximols oromucosal spray is currently the only cannabis-based prescription that delivers standardised dosage of CBD/THC in a 1:1 ratio with extensive research
• Tinctures and lozenges intermediate onset with limited research
Other routes
• Topicals ideal for localised symptoms (dermatological conditions, arthritis), with limited research evidence
• Suppositories possibly indicated for specific populations (cancer, GI symptoms, young/ elderly, etc.) with variable absorption. THChemisuccinate may allow for best absorption with limited research.
• Recreational routes include ‘shatter’, ‘dabs’, concentrates. Deliver very high doses of THC with high risk of euphoria, impairment, reinforcement, toxic psychosis, orthostatic hypotension. Inappropriate for medical application.
| The way of dosing | Smoking/Vaporizing | Oral | oral mucosal absorption | Topical administration |
| Onset of Effect/min | 5-10 | 60-180 | 15-45 | It depends on the situation |
| Time/h | 2-4 | 6-8 | 6-8 | It depends on the situation |
| Advantages | Fast-acting, for acute or paroxysmal symptoms (nausea/pain) | Less odor, easy to disperse, beneficial to chronic disease symptoms | A pharmaceutical form (nabiximols) is available. Its efficacy and safety have been documented | Small systemic effect, good for local symptoms |
| Limitations | Requires dexterity, vaporizers can be expensive, and not all are portable | Takes a long time to work | Expensive, availability is spotty | Only local effect |
As cannabis-based medicines return to mainstream use, the proper delivery of drugs is also a key factor. Clinicians must have a deeper understanding of their pharmacology, dosage, and administration to maximize their therapeutic potential and minimize related problems. Correctly understand and apply cannabis drugs, deepen their research in the medical field, and overcome more medical problems.
Reference:
1.Russo EB. The pharmacological history of Cannabis. In: Pertwee R, editor. Handbook of cannabinoids. Oxford, United Kingdom: Oxford University Press; 2014. p. 23–43.
2.Russo EB. History of cannabis and its preparations in saga, science and sobriquet. Chem Biodivers 2007;4:2624–48.
3.Flachenecker, P.; Henze, T.; Zettl, U. K. Nabiximols (THC/CBD Oromucosal Spray, Sativex®) in Clinical Practice - Results of a Multicenter, Non-Interventional Study (MOVE 2) in Patients with Multiple Sclerosis Spasticity. Eur Neurol 2014, 71 (5–6), 271–279. https://doi.org/10.1159/000357427.
4.National Academies of Sciences Engineering and Medicine (U.S.). Committee on the health effects of marijuana: an evidence review and research agenda. The health effects of cannabis and cannabinoids: the current state of evidence and recommendations for research. 5.Washington, DC: the National Academies Press; 2017. p. 1. (online resource, xviii, 468 pages). 6. Devinsky O, Cross JH, Laux L, Marsh E, Miller I, Nabbout R, et al. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl J Med 2017;376:2011–20.
7. Leweke FM, Piomelli D, Pahlisch F, Muhl D, Gerth CW, Hoyer C, et al. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatry 2012;2:e94.
8. Hill MN, Bierer LM, Makotkine I, Golier JA, Galea S, McEwen BS, et al. Reductions in circulating endocannabinoid levels in individuals with post-traumatic stress disorder following exposure to the World Trade Center attacks. Psychoneuroendocrinology 2013;38:2952–61.
9. Volicer L, Stelly M, Morris J, McLaughlin J, Volicer BJ. Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer's disease. Int J Geriatr Psychiatry 1997;12:913–10.Bergamaschi MM, Queiroz RH, Chagas MH, de Oliveira DC, De Martinis BS, Kapczinski F, et al. Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naive social phobia patients. Neuropsychopharmacology 2011;36:1219–26.
11.MacCallum, C. A.; Russo, E. B. Practical Considerations in Medical Cannabis Administration and Dosing. European Journal of Internal Medicine 2018, 49, 12–19. https://doi.org/10.1016/j.ejim.2018.01.004.
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