May 2010: Increased Pulmonary Function with Switch to Vaporized Cannabis. (SUNY; Albany, New York)

First some background: When solid particles are burned, they release a variety of molecules as smoke due to the addition of energy in the form of fire. With this addition of energy, a series of chemical reactions occur that release liquid particles and gases that often are of different composition than the original compound. Most often, when an organic compound, such as cannabis, is burned, it emits gases such as carbon monoxide and hydrogen cyanide that may be harmful to the user. Aside from the stigma attached to the name, the potential harmful effects of smoke are one of the main reasons why marijuana is not widely accepted in the medical community. However, there are other ways of administration besides inhaling smoke, such oral or inhaling vapor. Vaporizers heat the cannabis to around 400⁰ F without burning the plant material, reaching the boiling point of most cannabinoids and releasing them in a mist, with not enough heat applied to release other, more harmful compounds.

The new information: In this experiment, twenty frequent cannabis smokers were used to determine the differential effects of inhaling smoke or vapor. The twenty smokers had previously reported at least two respiratory side-effects and were asked to self-report their severity of symptoms. Additionally, their forced expiratory volume (FEV1) and forced vital capacity (FVC) were measured. FEV1 refers to the maximum volume of air that can be exhaled in 1 second, and FVC refers to the total volume of air that the lung can hold. The smokers were then switched to using vaporizers for one month and the measurements were repeated. Initially, average self-reported symptoms were graded to be 26.1, FVC was 4.54L, and FEV1 was 3.22L; after 1 month of vaporizer use, average self-reported symptoms dropped to 6.92, FVC was 4.76L, and FEV1 was 3.6L. The study used 8 males and 4 females (8 of the subjects ended up smoking during the 1 month period) with an average age of 20 years. For these figures, the normal values for FVC and FEV1 should be 4.89 and 4.06L respectively. It should also be noted that approximately a quarter (3) of the subjects also reported tobacco use.

What this means: The results of this experiment indicate that utilizing vaporized cannabis instead of smoke may improve respiratory side-effects and overall pulmonary function. Additionally, this study only represented the improvement after one month of switching to vaporized cannabis, and improvements may increase with an increased time interval. Therefore, utilizing cannabis in vaporized form is significantly safer than smoking it.

Earleywine, M. and Van Dam, N.T. “Pulmonary Function in Cannabis Users: Support for a Clinical Trial of the Vaporizer.” The International Journal on Drug Policy. (2010): preprint.

May 2010: Cannabinoids do not cause oxidative stress as previously thought. (Universidade do Porto; Porto, Portugal)

First some background: In order for human beings to survive, they must consume oxygen. This oxygen consumption drives the most basic of metabolic processes, allowing us to efficiently utilize carbohydrates, proteins, and fats as cellular sources of energy. The final conversion of these molecules to energy occurs within a cellular organelle known as the mitochondria. Within the mitochondria, oxygen is reduced and coupled with hydrogen to produce water, and a resulting hydrogen gradient drives the formation of ATP (cellular energy). However, this process is slightly inefficient, as some of the reduced oxygen fails to couple with hydrogen and become reactive oxygen species, such as superoxide. These reactive oxygen species may cause damage to a cell’s DNA, RNA, or proteins, but are normally converted by a series of enzymes (e.g. superoxide dismutase) into non-reactive molecules. Oxidative stress occurs when the balance between reactive species formation and conversion are disrupted, causing an accumulation of reactive oxygen species and an increase in cellular damage. Reactive oxygen species may also be formed as a byproduct of several other processes such as drug metabolism by cytochrome P450 enzymes. ∆⁹-Tetrahydrocannabinol (THC) has been previously reported to cause oxidative stress due to an increase in reactive oxygen species formation.¹

The new information: In this experiment, mice were injected with either THC, vehicle (the contents of the THC injection without the actual THC), or nothing. The mice livers were then analyzed for the activity level of enzymes that interact with reactive oxygen species: superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase, and glutathione peroxidase. Additionally, the biomarkers indicating oxidative stress in the mouse liver were lipid peroxidation, protein carbonylation, and DNA oxidation. The results showed that THC caused no change in the activity levels of all 5 enzymes and no biomarkers for oxidative stress were observed. Additionally, the vehicle actually caused an increase in glutathione peroxidase activity, indicating an increase in levels of hydroperoxides, a type of reactive oxygen species. But in the THC injection, the glutathione peroxidase activity level was normal, indicating that THC actually reduced the level of oxidative stress caused by the vehicle.

What this means: This experiment shows that THC in fact does not cause oxidative stress in the liver, and disproves several theories that have been previously presented. This goes to further dispel some of the notions that cannabinoids are more harmful than beneficial for the patient. Additionally, by opposing the increase in glutathione peroxidase activity caused by the vehicle, THC may in fact be an antioxidant in the liver as it has been shown to be in the brain.² This indicates that cannabinoids may be beneficial in treating other liver diseases besides hepatitis C.

¹Sarafian, T.A., et al. “Oxidative Stress Produced by Marijuana Smoke. An Adverse Effect Enhanced by Cannabinoids.” American Journal of Respiratory Cell and Molecular Biology. 20.6(1999): 1286-93.

²Hampson, A.J., et al. “Cannabidiol and (−)Δ9-Tetrahydrocannabinol are Neuroprotective Antioxidants.” Proceedings of the National Academy of Sciences of the United States of America. 95.14(1998): 8268-73.

Pinto, C.E., et al. “Effect of (-)-Delta(9)-Tetrahydrocannabinoid on the Hepatic Redox State of Mice.” Brazilian Journal of Medical and Biological Research. 43.4(2010): 325-9.

May 2010: Cannabinoids may be used to target brain cancer cells. (University of the Basque Country; Leioa, Spain)

First some background: Brain cancer refers to the uncontrolled growth of cells in the brain, mainly neurons or glial cells. Glial cells refer to brain cells which do not actually conduct the signals that give rise to bodily function, but rather play a supportive role for neurons. When cancer arises from glial cells, such as oligodendrocytes, astrocytes, microglia, and ependyma, the tumor is referred to as a glioma. Malignant gliomas are the most prominent form of life-threatening brain cancer as well as one of the most aggressive forms of cancer known; thus although gliomas are not the most common, they are one of the most deadly cancers. Additionally, unlike lung or colon cancer, there are no known environmental factors that may cause brain cancer besides vinyl chloride or radiation, which the average person is not readily exposed to; and diagnosing brain cancer involves more expensive imaging techniques. These factors combined make gliomas one of the hardest forms of cancer to battle.

The new information: This experiment aimed to elucidate changes in cannabinoid receptor expression of gliomas. It was conducted by introducing antibodies raised against the receptors to human glial tumors and measuring the rate and levels at which the antibodies bound both cannabinoid receptor 1 and 2 (CB1 and CB2). It was found that in glioblastoma multiforme (the typical glioma), levels of CB1 were decreased by 43% and levels of CB2 were increased by 765% compared to a sample of normal, healthy brain tissue.

What this means: By altering levels of cannabinoid receptors, the brain cancer cells now differentiate themselves in terms of their response to cannabinoids. It has been widely documented that cannabinoids may induce cell apoptosis via CB2 receptors, and thus this astounding increase in CB2 receptor expression by gliomas make them far more susceptible to programmed cell death than other brain cells. Thus, levels of cannabinoids that would be safe for normal brain tissue would cause death in brain cancer cells. Therefore, cannabis may have potential therapeutic effects for those diagnosed with brain cancer, and more specifically, glioblastoma multiforme (GBM).

De Jesús, M.L., et al. “Opposite changes in cannabinoid CB1 and CB2 receptor expression in human gliomas.” Neurochemistry International. 56.6-7(2010): 829-33.