Chronic obstructive pulmonary disease (COPD) and Cannabis, as explained by a Scientist

Chronic obstructive pulmonary disease (COPD) is an illness characterized by increased production of mucus and chronic inflammation of the airways resulting in reduced respiratory capacity. The two primary forms of COPD are chronic bronchitis, which produces a long-term cough with mucus, and emphysema, which leads to the progressive deterioration of the alveoli, the air sacs that allow for gaseous exchange in the lungs.

All smoke irritates the lungs and aggravates COPD, but vaporized or ingested cannabis could potentially provide many benefits because of its anti-inflammatory, immunosuppressant, and bronchodilating (airway opening) qualities.

Bronchodilatory effects: Studies performed in the 1970’s at the University of California Los Angeles by Donald Tashkin have shown that both inhaled and orally ingested THC produce bronchodilation for up to two hours after administration[ref]Tashkin DP, Shapiro BJ, Frank IM. Acute effects of smoked marijuana and oral delta9-tetrahydrocannabinol on specific airway conductance in asthmatic subjects. Am Rev Respir Dis. 1974;109(4):420-8.[/ref].

Further investigations by the Respiratory Pharmacology Laboratory in Paris have shown that CB1 receptor activation inhibits contraction of the smooth muscle surrounding the lungs in a concentration-dependent fashion, offering a possible mechanism for acute bronchodilation associated with cannabis intake[ref]Grassin-delyle S, Naline E, Buenestado A, et al. Cannabinoids inhibit cholinergic contraction in human airways through prejunctional CB1 receptors. Br J Pharmacol. 2014;171(11):2767-77.[/ref]. Although smoked cannabis also has this effect, any kind of combustion creates other lung irritants that would be counterproductive for COPD treatment.

Suppression of the immune system: Those with COPD have a heightened immune response in the lungs and compounds in cannabis can lead to immunosuppression. Studies have shown that THC induces rapid mobilization of a specific subset of white blood cells that arise from bone marrow called myeloid-derived suppressor cells (MDSCs)[ref]Hegde VL, Nagarkatti M, Nagarkatti PS. Cannabinoid receptor activation leads to massive mobilization of myeloid-derived suppressor cells with potent immunosuppressive properties. Eur J Immunol. 2010;40(12):3358-71.[/ref]. These cells exert potent immunosuppressant properties by inhibiting the proliferation and activation of T-cells, a component of the body’s immune response.

Additional studies performed at the University of South Carolina School of Medicine support these findings, where they determined that the intraperitoneal (injection into the body cavity) application of THC causes changes in microRNA expression that promotes the suppression of the immune system[ref]Hegde VL, Tomar S, Jackson A, et al. Distinct microRNA expression profile and targeted biological pathways in functional myeloid-derived suppressor cells induced by Δ9-tetrahydrocannabinol in vivo: regulation of CCAAT/enhancer-binding protein α by microRNA-690. J Biol Chem. 2013;288(52):36810-26.[/ref]. Other findings using murine models have shown that intraperitoneal administration of THC results in a reduction of allergen-induced mucus production[ref]Reddy AT, Lakshmi SP, Reddy RC. Murine model of allergen induced asthma. J Vis Exp. 2012;(63):e3771.[/ref].

Anti-inflammatory effects: Cannabinoids have anti-inflammatory benefits through a variety of mechanisms. The acidic cannabinoids found in the raw plant (THCA, CBDA, etc.) have a greater anti-inflammatory capacity than their non-acidic counterparts (THC, CBD, etc.). Specifically studies by Ruhaak, et al., have shown that acidic cannabinoids are capable of inhibiting enzymes called cyclooxygenases (COX-1 and COX-2). These enzymes are responsible for the production of inflammatory molecules such as prostaglandins, which contribute to airway inflammation.

Recently studies performed at the University of Sao Paulo using cannabidiol (CBD) have also shown some potential for improving the symptoms of COPD. Using LPS, a component of the cell wall of gram-negative bacteria as an inflammatory agent, they showed the application of CBD resulted in decreased pulmonary inflammation and improvements in lung function in mouse models of inflammatory lung disease[ref]Ribeiro A, Almeida VI, Costola-de-souza C, et al. Cannabidiol improves lung function and inflammation in mice submitted to LPS-induced acute lung injury. Immunopharmacol Immunotoxicol. 2014;:1-7.[/ref].

Other studies of terpene compounds, the aromatic components found in cannabis show anti-inflammatory benefits as well. In particular, beta caryophyllene has been shown to act as a dietary cannabinoid, attenuating inflammatory responses in various tissues in a CB2 receptor-dependent fashion[ref]Bento AF, Marcon R, Dutra RC, et al. β-Caryophyllene inhibits dextran sulfate sodium-induced colitis in mice through CB2 receptor activation and PPARγ pathway. Am J Pathol. 2011;178(3):1153-66.[/ref].

Conclusion: These studies indicate that cannabis could potentially act as a means to mitigate acute attacks of airway constriction and may also act as a preventative measure for patients with COPD. However, human trials are needed to confirm some of these benefits and until restrictions on this kind of research are lifted, a deeper understanding of these mechanisms will remain poorly understood.