The global cannabis research effort is gaining momentum and new areas of research are emerging. Cannabidiol’s (CBD) therapeutic benefits remain a hot research topic, and some of these studies have now expanded to placebo-controlled human clinical trials. Others are moving beyond THC and CBD as scientists take a closer look at the effects of what are sometimes deemed “minor cannabinoids.” Plus, new ways of detecting THC in your fingerprints or your breath have been discovered, and there may be a dietary supplement that protects the fetal brain from THC in cannabis-consuming mothers.
Here are some of the most notable cannabis science stories from the second half of the year.
CBD can block fear-related memories from forming after a traumatic event
CBD is gaining support as a preventative strategy to protect against damage from a traumatic brain injury, but a recent study suggests that it may also help in preventing the long-term devastation from severe psychological trauma.These studies suggest that CBD may help prevent the development of PTSD by impairing the memory of a traumatic or stressful event.
PTSD results from exposure to a traumatic or stressful event. Scientists can model the events that cause PTSD in lab animals by pairing neutral sensory stimuli, like tones or lights, with a small shock delivered through the floor of a conditioning chamber. Soon, the animals become fearful of both the chamber where they received the shock and the stimuli that was associated with the shock.
Scientists in Brazil used this traumatic fear conditioning paradigm with rats to study CBD’s impact on the memory of the traumatic shock. CBD was injected directly into the hippocampus, a brain structure involved in autobiographical memory and regulating the stress response, at different time points following the traumatic event. Consistent with CBD’s protective effects, CBD injected into the hippocampus immediately after fear conditioning impaired memory for the event through a mechanism that required endocannabinoid receptors 1 and 2 (CB1 and CB2) and partially involved serotonin and adenosine receptors.
However, people don’t usually have access to preventative treatment in the moments immediately following a traumatic event. The scientists therefore sought to identify the timeframe by which CBD treatment would be effective. CBD’s benefits were only observed at 1 hour, but not 3 hours after the event.
Together, these studies suggest that CBD may help prevent the development of PTSD by impairing the memory of a traumatic or stressful event. Further, they extend support for CBD’s potential value as a preventative strategy for high-risk activities such as military combat. However, this benefit extends beyond the military as nearly 7% of the population experience PTSD symptoms from non-combat related events such as vehicle accidents or domestic violence. Many are eagerly awaiting studies that probe the CBD’s preventative benefits in a clinical trial.
Revealing the benefits of “minor” cannabinoids
Because THC and CBD are usually the most abundant cannabinoids produced by the plant, other cannabinoids are often deemed “minor,” but emerging evidence is pointing to their therapeutic benefits that are by no means “minor”.
In one study, Spanish scientists revealed weight-loss benefits of THCA-A (tetrahydrocannabinolic acid A) in a mouse model of diet-induced obesity. Mice fed a high-fat diet (45% fat) for 12 weeks gained three times more weight than those fed a standard diet (8.4% fat), had signs of metabolic dysfunction, fatty livers, and increased insulin levels. However, daily administration of THCA-A blocked weight gain, improved glucose tolerance and insulin levels, protected against a fatty liver, and increased the amount of higher calorie-demanding “brown fat.”
In another study, a team of scientists led by Israeli chemist, Raphael Mechoulam, identified wake-promoting effects of cannabidiolic acid (CBDA) in rats. They studied CBDA indirectly by using a more stable synthetic version of the cannabinoid produced in Dr. Mechoulam’s lab. Administration of CBDA increased wakefulness by around 50% by decreasing the amount of time the rats spent in slow-wave sleep without impacting time spent in the REM sleep stage (i.e., when humans experience vivid dreams). These effects were associated with increased levels of wake-promoting brain chemicals such as acetylcholine that helps promote attention in awake animals.
Both of these studies tested doses that are higher than those one would get from a traditional cannabis strain. However cannabinoid formulations can now be developed using isolates in optimized combinations and doses for specific conditions. Research efforts in the upcoming year will continue to pursue these optimized formulations, but knowing the impact of these individual cannabinoids is a critical first step.
Protecting the developing brain from THC exposure during pregnancy
Brain development is a tightly regulated process that is easily affected by environmental factors like drug use. Despite warnings against using cannabis during pregnancy, many women continue to use THC-rich cannabis as a remedy for morning sickness, depression, and anxiety.
In many cases, cannabis use during pregnancy is associated with behavioral problems in offspring, including attentional deficits, cognitive challenges, social withdrawal, and sensory-gating impairments. Many of these effects can be attributed to impaired development of inhibitory brain cells by THC. Behavioral impairments were either not observed, or of lowest severity, in the cannabis-using mothers with the highest choline levels.
There currently aren’t any prenatal treatment strategies to block THC’s effects on the developing brain, but gestational nutrient levels may provide insight into protective mechanisms against the consequences of prenatal THC exposure.
Prenatal nutrient treatment has already been studied and utilized clinically for other conditions such as choline to prevent birth defects in alcoholic mothers. Choline is an essential nutrient found in many foods—eggs, liver, meat, and potatoes are especially rich. The body can actually produce its own choline, but it’s not enough and must be augmented through diet. This is particularly the case in pregnancy since the developing brain requires choline.
Choline is needed to activate a type of brain receptors, called nicotinic acetylcholine receptors that have a 10-fold greater expression level early in gestation than in adulthood. Importantly, they’re also found on some of the same brain cells where CB1 receptors (i.e., targets for THC) are expressed.
Scientists working out of Denver, Colorado recently completed their assessment of maternal choline levels on the behavioral effects from prenatal cannabis exposure. Since 2013, they tracked maternal choline levels at 16 weeks of gestation in over 130 women, and their newborns were assessed at 1 and 3 months after birth. Maternal cannabis use during the first 10 weeks of gestation was associated with reduced self-regulation, attention span, cuddliness, and bonding with parents. However, these behavioral impairments were either not observed, or of lowest severity, in the cannabis-using mothers with the highest choline levels.
While this study is by no means a green-light to use cannabis during pregnancy, it does expose a potential benefit of high levels of dietary choline and provides some of the first evidence for an interventional strategy to prevent THC’s harmful effects on the developing brain.
Rapid detection of THC in the breath or fingerprints
One of the commonly reported sticking points among those who oppose cannabis legalization (and even those who support it) is the concern over driving while stoned.
Most are aware of the dangers of driving while intoxicated by alcohol. Even low levels of alcohol impair processing by the brain’s cerebellum, a critical region that’s responsible for making balanced and coordinated movements, improving reaction time, and regulating attention. Importantly, the cerebellum is also enriched with THC’s primary intoxicating target, CB1 receptors.
In part through THC’s action on CB1 receptors in the cerebellum, cannabis can decrease a driver’s ability to safely drive a car or make quick reactions on the road. Even so, 70% of respondents to a survey by the American Automobile Association said that they’d feel confident that they wouldn’t be caught driving while stoned, and perhaps that’s why 14.8 million drivers reported driving within one hour after using cannabis in the last month. More dangerous roads because of stoned drivers does a disservice to the global legalization movement.
Unsurprisingly, much has been invested in trying to develop rapid detection methods for THC that mimic the speed and accuracy of the breathalyzer test for alcohol. Differences in the molecular properties between alcohol and THC makes it so the same technology cannot be used to detect both, but recent advances indicate that a rapid and non-invasive THC detection method is on the horizon.
One team of scientists out of the University of Pittsburgh have developed a THC breathalyzer that uses tiny carbon nanotubes, 100,000 times smaller than a human hair. The small percentage of THC that’s lost through one’s breath binds to the tubes and changes their electrical properties in a specific manner that signals THC is present. Despite the impressive scientific advancement from these two studies, it remains unclear what levels of THC or THC-COOH actually lead to intoxicated driving.
Another team out of the University of Albany State has discovered a method of detecting the THC metabolite, THC-COOH, from fingerprints. We traditionally think of fingerprints analysis as the assessment of loops and whorls, but now, but it has shifted to chemical composition in recent years. In fact, there’s nothing particularly special about fingerprints, per se, in conveying information about THC consumption. Instead, fingerprints are a source of chemicals found in sweat. Analyzing THC-COOH in sweat is far less invasive than collecting blood or urine, and you don’t need much. These scientists discovered a method that uses antibodies that bind to THC and THC-COOH. If either of these are present, there will be a change in the color of a particular dye. It may take longer than the breathalyzer, but its accuracy warrants further investigation.
Despite the impressive scientific advancement from these two studies, it remains unclear what levels of THC or THC-COOH actually lead to intoxicated driving. The 0.08% blood alcohol level that determines impaired driving stemmed from a political compromise and not an empirical scientific pursuit. Likely, the same will be true for THC, regardless if we can detect it in our breath or fingerprints.
New directions for CBD clinical trials
People use CBD for a wide range of symptoms, from pain to anxiety. Until recently, and with the exception of pediatric epilepsies, the clinical trials that provide empirical evidence for its use has been limited to small-scale or open-label trials.
In open-label trials, both the consumer and their physician know that they’re using the experimental drug. This open-label trial design allows for bias because expectation alone can influence outcomes. These important limitations have slowed the clinical adoption of CBD treatment approaches for many conditions where pre-clinical evidence is plentiful and where many people report that CBD relieves their symptoms.
To eliminate potential bias from creeping into a study, a double-blinded placebo-controlled study is the gold standard. Here, both the patient and their physician don’t know whether the treatment is a placebo or CBD. By moving towards double-blinded placebo-controlled CBD trials, this important facet of cannabis-based medicine will start to get more respect from the medical community, and promising findings will be more likely to lead to real change in pharmacological treatment strategies and health insurance coverage.
In the second half of 2019, several double-blind placebo-controlled CBD trials were published that extend beyond its treatment of epilepsy and autism. One study out of Poland found that CBD, applied topically twice daily at a concentration of 67 mg CBD/ml, helps relax jaw muscles and reduce pain in people who suffer from myofascial pain. Since the pain usually results from muscle damage due to excessive clenching, CBD represents an effective and non-addicting approach to localized muscle relaxation and decreased pain.
Another study conducted in the US also studied the effect of topical CBD on pain management, but this time in peripheral nerve damage. Damage to these nerves, often due to disease, may cause them to send erroneous signals to the brain which is interpreted as pain. Here, CBD (83 mg CBD/ml) applied to the painful site reduced intense pain, sharp pain, and reduced cold/itchy sensations that are commonly experienced in patients with peripheral neuropathies. Notably, there were no adverse effects reported, and given that the average age of participants was 68, this study suggests that CBD may be a safe and effective treatment for peripheral nerve pain throughout all stages of adulthood.
Lastly, CBD’s anxiety-reducing effects were tested in Japanese teenagers with social anxiety disorder (SAD). Participants who consumed pills of 300mg CBD daily for four weeks had lower scores on both measures of social anxiety than those who took placebo pills. This study extends CBD’s the anxiety-reducing benefits that had previously been observed in healthy volunteers (e.g., during simulated public speaking) or following a single dose in patients with SAD, and indicates that it may be an effective daily treatment strategy of SAD in teenagers and young-adults.
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