All results and statistics are directly quoted from the NIH (https://www.drugabuse.gov/publications/drugfacts/marijuana-medicine) (marijuana) and directly from a presentation on the NIH site (https://www.drugabuse.gov/about-nida/legislative-activities/testimony-to-congress/2016/biology-potential-therapeutic-effects-cannabidiol) (CBD), as to preserve any bias to be examined in following posts.

Research: On marijuana (not components: i.e. THC & CBD)

Clinical Research

Rodent Models

  • Recent animal studies have shown that marijuana extracts may help kill certain cancer cells and reduce the size of others. Evidence from one cell culture study with rodents suggests that purified extracts from whole-plant marijuana can slow the growth of cancer cells from one of the most serious types of brain tumors. Research in mice showed that treatment with purified extracts of THC and CBD, when used with radiation, increased the cancer-killing effects of the radiation.
  • Studies in rats also show that adolescent exposure to THC is associated with an altered reward system, increasing the likelihood that an animal will self-administer other drugs (e.g., heroin) when given an opportunity
  • As people age, they lose neurons in the hippocampus, which decreases their ability to learn new information. Chronic THC exposure may hasten age-related loss of hippocampal neurons. In one study, rats exposed to THC every day for 8 months (approximately 30 percent of their lifespan) showed a level of nerve cell loss at 11 to 12 months of age that equaled that of unexposed animals twice their age.
  • Early exposure to cannabinoids in adolescent rodents decreases the reactivity of brain dopamine reward centers later in adulthood. To the extent that these findings generalize to humans, this could help explain the increased vulnerability for addiction to other substances of misuse later in life that most epidemiological studies have reported for people who begin marijuana use early in life. It is also consistent with animal experiments showing THC’s ability to “prime” the brain for enhanced responses to other drugs. For example, rats previously administered THC show heightened behavioral response not only when further exposed to THC but also when exposed to other drugs such as morphine—a phenomenon called cross-sensitization.
    • These findings are consistent with the idea of marijuana as a “gateway drug.” However, the majority of people who use marijuana do not go on to use other, “harder” substances. Also, cross-sensitization is not unique to marijuana. Alcohol and nicotine also prime the brain for a heightened response to other drugs and are, like marijuana, also typically used before a person progresses to other, more harmful substances.

Human models:

  • Imaging studies of marijuana’s impact on brain structure in humans have shown conflicting results.
    • Some studies suggest regular marijuana use in adolescence is associated with altered connectivity and reduced volume of specific brain regions involved in a broad range of executive functions such as memory, learning, and impulse control compared to people who do not use.
    • Other studies have not found significant structural differences between the brains of people who do and do not use the drug.

Therefore, there are no conclusive results about marijuana’s effect on brain connectivity and volume.

Statistics:

Driving and Accidents:

  • Those involved in vehicle crashes with THC in their blood, particularly higher levels, are three to seven times more likely to be responsible for the incident than drivers who had not used drugs or alcohol
  • Several meta-analyses of multiple studies found that the risk of being involved in a crash significantly increased after marijuana use—in a few cases, the risk doubled or more than doubled. However, a large case-control study conducted by the National Highway Traffic Safety Administration found no significant increased crash risk attributable to cannabis after controlling for drivers’ age, gender, race, and presence of alcohol.
  • The Drug Abuse Warning Network (DAWN), a system for monitoring the health impact of drugs, estimated that in 2011, there were nearly 456,000 drug-related emergency department visits in the United States in which marijuana use was mentioned in the medical record(a 21 percent increase over 2009). About two-thirds of patients were male and 13 percent were between the ages of 12 and 17. It is unknown whether this increase is due to increased use, increased potency of marijuana (amount of THC it contains), or other factors.
    • Marijuana potency, as detected in confiscated samples, has steadily increased over the past few decades. In the early 1990s, the average THC content in confiscated marijuana samples was roughly 3.7 percent. In 2014, it was 6.1 percent. Also, newly popular methods of smoking or eating THC-rich hash oil extracted from the marijuana plant (a practice called dabbing) may deliver very high levels of THC to the person. The average marijuana extract contains more than 50 percent THC, with some samples exceeding 80 percent.

But…

  • A large case-control study conducted by the National Highway Traffic Safety Administration found no significant increased crash risk attributable to cannabis after controlling for drivers’ age, gender, race, and presence of alcohol.

Therefore there are no conclusive results about marijuana’s effect on accident prevalence.

Dependence (addiction)

  • People who begin using marijuana before the age of 18 are four to seven times more likely to develop a marijuana use disorder than adults.
  • Marijuana use disorders are often associated withdependence—in which a person feels withdrawal symptoms when not taking the drug. People who use marijuana frequently often report irritability, mood and sleep difficulties, decreased appetite, cravings, restlessness, and/or various forms of physical discomfort that peak within the first week after quitting and last up to 2 weeks. Marijuana dependence occurs when the brain adapts to large amounts of the drug by reducing production of and sensitivity to its own endocannabinoid neurotransmitters.

Brain Damage?

  • A large longitudinal study in New Zealand found that persistent marijuana use disorder with frequent use starting in adolescence was associated with a loss of an average of 6 or up to 8 IQ points measured in mid-adulthood. Significantly, in that study, those who used marijuana heavily as teenagers and quit using as adults did not recover the lost IQ points.

Socioeconomic Effects

  • One study among postal workers found that employees who tested positive for marijuana on a pre-employment urine drug test had 55 percent more industrial accidents, 85 percent more injuries, and 75 percent greater absenteeism compared with those who tested negative for marijuana use.
  • One study, for example, compared people involved with current and former long-term, heavy use of marijuana with a control group who reported smoking marijuana at least once in their lives but not more than 50 times. All participants had similar education and income backgrounds, but significant differences were found in their educational attainment: Fewer of those who engaged in heavy cannabis use completed college, and more had yearly household incomes of less than $30,000. When asked how marijuana affected their cognitive abilities, career achievements, social lives, and physical and mental health, the majority of those who used heavily reported that marijuana had negative effects in all these areas of their lives

Research: On CBD alone

  • CBD, cannabidiol, is a component of marijuana that is a major component of marijuana (depending on the strain) and does not produce any effects of intoxication of euphoria. It therefore is not mind-altering in any way as far as we know—its effects are systemic and not noticeable to the consciousness.

What we know:

Treatment for seizures (epilepsy)

  • A number of studies over the last two decades or more have reported that CBD has anti-seizure activity, reducing the severity of seizures in animal models.vi,viiIn addition, there have been a number of case studies and anecdotal reports suggesting that CBD may be effective in treating children with drug-resistant epilepsy. However, there have only been a few small randomized clinical trials examining the efficacy of CBD as a treatment for epilepsy; the total number of subjects enrolled in these studies was 48. Three of the four studies reported positive results, including decreased frequency of seizures. However, the studies suffered from significant design flaws, including failure to fully quantify baseline seizure frequency, inadequate statistical analysis, and a lack of sufficient detail to adequately evaluate and interpret the findings. Therefore, the currently available information is insufficient to draw firm conclusions regarding the efficacy of CBD as a treatment for epilepsy; a recent Cochrane review concluded, there is a need for “a series of properly designed, high quality, and adequately powered trials.”

Neuroprotectivity

  • CBD has also been shown to have neuroprotective properties in cell cultures as well as in animal models of several neurodegenerative diseases, including Alzheimer’s, stroke, glutamate toxicity, multiple sclerosis (MS), Parkinson’s disease, and neurodegeneration caused by alcohol abuse.  Nabiximols (trade name Sativex), which contains THC and CBD in roughly equal proportions, has been approved throughout most of Europe and in a number of other countries for the treatment of spasticity associated with MS. It has not been approved in the United States, but clinical trials are ongoing, and two recent studies reported that nabiximols reduced the severity of spasticity in MS patients. There have been limited clinical trials to assess the potential efficacy of CBD for the other indications highlighted; however, a recent small double-blind trial in patients with Parkinson’s disease found the CBD improved quality-of-life scores.
    • Speculated to add to analgesic effects of THC via reducing inflammation

Anti-tumor effects

  • In addition to the research on the use of cannabinoids in palliative treatments for cancer—reducing pain and nausea and in increasing appetite—there are also several pre-clinical reports showing anti-tumor effects of CBD in cell culture and in animal models. These studies have found reduced cell viability, increased cancer cell death, decreased tumor growth, and inhibition of metastasis (reviewed in McAllister et al, 2015). These effects may be due to the antioxidant and anti-inflammatory effects of CBD; however these findings have not yet been explored in human patients. There are multiple industry sponsored clinical trials underway to begin to test the efficacy of CBD in human cancer patients.

Treatment for anxiety

  • CBD has shown therapeutic efficacy in a range of animal models of anxiety and stress, reducing both behavioral and physiological (e.g., heart rate) measures of stress and anxiety. In addition, CBD has shown efficacy in small human laboratory and clinical trials. CBD reduced anxiety in patients with social anxiety subjected to a stressful public speaking task. In a laboratory protocol designed to model post-traumatic stress disorders, CBD improved “consolidation of extinction learning”, in other words, forgetting of traumatic memories. The anxiety-reducing effects of CBD appear to be mediated by alterations in serotonin receptor 1a signaling, although the precise mechanism remains to be elucidated and more research is needed. 

CBD as an anti-psychotic drug and for treatment of substance abuse disorders has also been investigated but is even more inconclusive than the research presented above.

Conclusions:

There is not enough abundance or quality of research carried out on either whole marijuana or CBD alone to make any clear statements about either one in regards to its safety (health effects) and certainly not to prescribe it as a drug, yet 2 FDA-approved anti-nausea drugs are currently in use that contain THC for treatment of chronic AIDS wasting syndrome. This incongruency is due to the fact that quality research requires repetitive trials and therefore adequate funding. Since the government has made it difficult for studies not based on finding negative effects of marijuana, through lack of funding for truly inquisitive research, to enforce its classification as a schedule 1 drug and also due to the difficulty of obtaining marijuana (since it is a schedule 1 drug) we can make no clear declarations about the benefits nor detriments of marijuana use, from a medical standpoint. Next week I will explore the socio-political factors that created this research difficulty and caused marijuana to become designated as a schedule 1 drug

Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s