Adverse Health Effects Of Recreational Cannabis Use

Background: Cannabis plants produce a unique family of terpeno-phenolic compounds called cannabinoids, which produce the "high" one experiences from consuming marijuana. Cannabis is usually smoked in a ‘joint’ or with a water pipe (sometimes with tobacco added) because smoking is the most efficient way to achieve the desired psychoactive effects.

Two Major Constituents of Cannabis. THC is psychoactive.

A quick summary for all:

1. There are 483 identifiable chemical constituents known to exist in the cannabis plant, and at least 85 different cannabinoids have been isolated from the plant.

2. The two cannabinoids usually produced in greatest abundance are cannabidiol (CBD) and/or delta-9-tetrahydrocannabinol (THC), but only THC is psychoactive or gives “high”.

3. Since the early 1970s, Cannabis plants have been categorized by their chemical phenotype or "chemotype", based on the overall amount of THC produced, and on the ratio of THC to CBD. Although overall cannabinoid production is influenced by environmental factors, the THC/CBD ratio is genetically determined and remains fixed throughout the life of a plant.

4. Non-drug plants produce relatively low levels of THC and high levels of CBD, while drug plants produce high levels of THC and low levels of CBD. When plants of these two chemotypes cross-pollinate, the plants in the first filial (F1) generation have an intermediate chemotype and produce similar amounts of CBD and THC. Female plants of this chemotype may produce enough THC to be utilized for drug production.

Recreational Use:

Cannabis is used for a wide variety of purposes including recreational use, medical use and as hemp fibre. Many human culture including Chinese, Indian and Greek, etc., have records of cannabis use in various social and religious activities. Cannabis is a popular recreational drug around the world, only behind alcohol, caffeine and tobacco, and it is also available as baked product and as a tea!!!

Summary: The article reports analysis of various “side-effects” that have been associated with ‘heavy’ or ‘regular’ cannabis, which for the study purpose is defined as daily or near-daily use. Starting from year 1993 till year 2013, a comparison of the evidence in 1993 with the evidence and interpretation of the same health outcomes in 2013 is attempted. Various fallouts including health, social behaviors, education, etc. are evaluated for regular user vis-à-vis a non-regular/non-user.

Results: The key conclusions are:

Adverse Effects of Acute Cannabis Use

1. Cannabis does not produce fatal overdoses.

2. Driving while cannabis-intoxicated doubles the risk of a car crash; this risk increases substantially if users are also alcohol-intoxicated.

3. Cannabis use during pregnancy slightly reduces birth weight of the baby.

Adverse Effects of Chronic Cannabis Use

1. Regular cannabis users can develop a dependence syndrome, the risks of which are around 1 in 10 of all cannabis users and 1 in 6 among those who start in adolescence.

2. Regular cannabis users double their risks of experiencing psychotic symptoms and disorders, especially if they have a personal or family history of psychotic disorders, and if they start using cannabis in their mid-teens.

3. Regular adolescent cannabis users have lower educational attainment than non-using peers but researchers don't know whether the link is causal.

4. Regular adolescent cannabis users are more likely to use other illicit drugs, but researchers don't know whether the link is causal.

5. Regular cannabis use that begins in adolescence and continues throughout young adulthood appears to produce intellectual impairment, but the mechanism and reversibility of the impairment is unclear.

6. Regular cannabis use in adolescence approximately doubles the risk of being diagnosed with schizophrenia or reporting psychotic symptoms in adulthood.

7. Regular cannabis smokers have a higher risk of developing chronic bronchitis.

8. Cannabis smoking by middle aged adults probably increases the risk of myocardial infarction.

Article Citation: Hall, W. What has research over the past two decades revealed about the adverse health effects of recreational cannabis use? Addiction 2015, 110(1), 19-35. (free copy)

Cannabidiol in Asthma Treatment: Now Mice Later Men?

Cannabinoids are components of the Cannabis sativa (marijuana) plant and are known to exert potent anti-inflammatory, immunomodulatory, and analgesic effects through activation of cannabinoid-1 and cannabinoid-2 (CB1 and CB2) receptors located in the central nervous system (CNS) and immune cells, respectively. Cannabidiol (CBD) is the main nonpsychotropic cannabinoid and reported to have beneficial effects in many pathological conditions, including neuropsychiatric disorders and brain inflammatory diseases, without having significant activity on CB1 and CB2 receptors.

Asthma is a disorder of the conducting airways, which contract too much and too easily both spontaneously and in response to a wide range of exogenous and endogenous stimuli. This airway hyper-responsiveness is accompanied by enhanced sensory irritability of airways and increased mucus secretion. Classically, asthma is characterized by chronic airway inflammation and remodeling, hyper-responsiveness, and increase of T-helper cell 2 levels- (Th2-) related cytokines.

Taking a clue form various published results that CBD was shown to have potent immunosuppressive and anti-inflammatory properties, researchers developed a mouse model where they were able to prove protective effect of CBD upon inflammatory response in an animal model of asthma. Researchers determined the levels of 6 cytokines implicated in asthma, which can be divided by the response profiles Th1 (TNF-α and IL-6) and Th2 (IL-4, IL-13, IL-10, and IL-5). Asthma induction resulted in an increase in all cytokines levels when compared to control animals. CBD treatment was able to decrease both Th1 and Th2 cytokines.

Study Design: Rats were immunized by an i.p. injection of 10 µg of chicken ovalbumin (OVA) in 100 µL of aluminum hydroxide (alum) or alum alone. After 14 days, rats were boosted with OVA or alum. Seven days later, rats received aerosol challenges (30 min/for 3 days) with 1% OVA or saline. CBD was suspended in 2% of polyoxyethylenesorbitan monooleate (Tween 80). The solutions were prepared immediately before use and were protected from light during the experimental session. CBD was administered i.p. once a day during the last two days of the OVA challenge at the dose of 5 mg/kg.

All treatments were administered in a volume of 1 mL/kg of CBD or vehicle. For this experiment, 21 rats were used, which were randomly divided into three groups: vehicle (control) (n = 7), OVA + vehicle (asthma control) (n = 7), and OVA + CBD (asthma + treatment) (n = 7). Blood samples were obtained 24 hours after the last challenge by decapitation to determine the levels of cytokines.

Important clinical findings using a mice model:

1. CBD treatment significantly decreased the levels of cytokines involved in the immune response to an allergen, such as IL-4 and IL-5: IL-4 is responsible for the inhibition of Th1 cells differentiation and for Th2 cells differentiation and expansion and has an important role in IgE production. In addition, IL-4 seems to be a requisite for T lymphocytes to produce IL-5. IL-5 is essential for the maturation of eosinophils, and it accumulates in the lung during the inflammatory process of asthma.

2. IL-13 was reduced by CBD administration: IL-13 is considered a major stimulus for mucus hypersecretion, an important characteristic of asthma, which contributes to the exacerbation of symptoms.

3. CBD is able to decrease IL-6 levels: IL-6 levels are increased in sputum and systemic circulation in severe asthmatic patients, which can be responsible for the raise of C-reactive protein circulation in these patients.

4. CBD reduced the levels of TNF-α: TNF-α is a major mediator of severe asthma.

The authors were also candid is pointing outs some limitations on their part in not been able to measure lung function and the effect of CBD in bronchoalveolar lavage fluid cytokines, but they are sure that these results can act as a guide for future experiments.

Article citation: Dal-Pizzol, F.; et. al. Evaluation of Serum Cytokines Levels and the Role of Cannabidiol Treatment in Animal Model of Asthma. Mediators Inflamm 2015, 538670.