CBD Benefits: Evidence From Over 70 Human Studies
CBD is great and I personally love it, so i’ll admit my bias towards it straight off the bat. But today I want to do it justice, by taking a look at what the scientific evidence says about what it can and can’t do.
There are countless anecdotes about how CBD has helped people, but not enough studies to substantiate those claims (yet).
If it works, it works. That’s great for most people.
But for CBD to gain real credibility, studies are needed to separate actual benefits from false claims. They’ll also help to dissolve a cure-all mentality around CBD.
We’re going to take a deep dive into the existing evidence around CBD, and what it is (and isn’t) showing promise for.
Using the evidenced based medicine hierarchy, we can rank the quality of evidence around CBD to assess its benefits.
Just as a disclaimer, it isn’t a perfect way of evaluating evidence, as the quality of an individual study can outweigh what type of study it is in the rankings.
But on the whole it can be helpful to organise evidence (and assess benefits) as a rule of thumb.
CBD Benefits: How are there so many?
CBD mimics compounds we naturally produce in our bodies called endocannabinoids.
Endocannabinoids are like messengers. They are constantly delivering and receiving information around the body to keep it in balance.
Just like hormones.
They run the show, from pain to pregnancy, they do it all. Think of endocannabinoids as conductors of the orchestra that is your body. They keep all the bodily systems, which are like instruments, playing in health giving harmony.
Endocannabinoid levels can fall or rise in the body, and that’s where harmony is lost, and disease can start to set in. When they exist within a sweet spot, so do we.
CBD can buffer against both high or low levels of endocannabinoids, helping to restore harmony across bodily systems and the body as a whole.
This is why CBD can have a potentially powerful effect in SO many diseases.
It’s not sorcery, it’s science.
Studies on CBD (ranked highest to lowest)
Again, the best study types can still be conducted poorly, so just bear in mind that there is crossover between the quality of evidence an RCT can give you vs a case control study for example.
Meta-Analyses of RCT’s
- Epilepsy (*)
- RDB Epilepsy (*), (*), (*), (*)
- RDB Pain (*), (*)
- RDB Psychosis (Schiz) (*), (*)
- RDB Type II Diabetes (*)
- RDB Huntington’s (*)
- RDB Anxiety (*), (*)
- RDB Multiple Sclerosis (*), (*)
- RDB Hypertension (*)
- RDB Crohn’s (*)
- RDB Ulcerative Colitis (*)
- RDB Smoking addiction (*)
- RDB Alcohol intoxication / addiction (*)
- RDB Opioid Addiction (*)
- RDB Myofascial Pain (*)
- RDB Leaky gut (*)
- RDB Neuropathic pain (topical CBD) (*)
- RDB cannabis dependence (*)
- RDB Parkinsons (*), (*)
- RCO Fibromyalgia (pain) (*)
- RCT Fatty Liver Disease (*)
- RCT THC induced memory loss and paranoia (*)
- Cancer related symptoms (with THC, CBD alone coming) (*), (*)
- Osteoarthritis (*), (*)
Clinical Trials (Experimental)
- DB trials Anxiety (*), (*)
- DB Parkinsons (*)
- CT Insomnia (*)
- Open label epilepsy (*), (*), (*), (*), (*), (*), (*)
- Open label psychosis (*)
- Open label Huntington’s (*)
- Open label neuroprotection (*)
- Open label cannabis induced psychosis and cognitive impairment (*)
- Pilot trial 0.4% THC + 9% CBD cannabis and headache (*)
Meta analyses of Observational Studies
- Treatment resistant epilepsy (*)
Cohort Studies (Observational)
- Open label pain (*)
- Cannabis dependence (*)
- Epilepsy (*), (*), (*), (*)
- Psoriasis and Dermatitis (*)
- Autism (*)
- Epidermolysis bullosa (skin blistering) (*)
- Epilepsy (retrospective) (*)
- Autism (retrospective) (*)
- Cancer (retrospective) (*)
- Dysautonomic syndrome (*)
Cross-sectional studies (Observational)
- Pain, anxiety, depression (top 3 reasons for use) (*)
- Pain, mood, sleep and general wellness (*)
- Autoimmune hepatitis (pain, sleep, fatigue) (*)
- Stress, anxiety and sleep (*)
Case Series (Observational)
- PTSD (and symptoms) (11)
- Bi-polar (*)
- Anxiety and sleep (*)
- Cannabis Withdrawal, Anxiety and Depression (*)
- Cannabis Withdrawal, Anxiety and Sleep (*)
- PTSD, Sleep and anxiety (*)
- Lung cancer (*)
- Ovarian cancer (*)
- Cancer (*)
- Treatment resistant schizophrenia (*)
- ALS (*)
- Dystonia (*)
- Brain tumour related epilepsy (*)
- REM Sleep Disorder (*)
- Depression (*)
CBD & Epilepsy
The most robust and widespread research with CBD has been concerned with Epilepsy. There’s been quite a few randomised, double blind controlled trials with large samples (groups of people) in both children and adults.
Neuronal function can be disrupted in epilepsy leading to seizures. CBD helps to normalise the way neurones fire by pushing a few buttons in the brain.
- Restore calcium homeostasis (helping neurones fire effectively)
- Calm overactive neurones by boosting GABA
- Regulate the brain’s response to serotonin (which influences seizures)
- Buffer endocannabinoid signalling
The studies have shown that CBD can reduce both the amount of seizures and their severity, which improves quality of life of those with epilepsy.
|Randmised Controlled Trials||Cunha et al., 1980||Secondary generalized epilepsy||2-300mg||15||4.5 months||4 almost totally convulsant free, 3 partially reduced, 1 no change. No imporvement in placebo group.|
|Devinsky et al., 2018||Lennox-Gastaut Syndrome||10-20mg/kg body weight||225||14 weeks||37.2% - 41.9% reduction in seizure frequency compared to only 17.2% in placebo group.|
|Thile et al., 2018||Lennox-Gastaut Syndrome||20mg/kg body weight||171||14 weeks||Significantly reduced monthly seizure frequency compared to placebo (43.9% vs 21.8%)|
|Devinsky et al., 2017||Dravet syndrome||20mg/kg body weight||120||14 weeks||43% of patients had at least a 50% reduction in convulsive-seizure frequency with CBD, vs 27% with placebo.|
|Clinical Trials||Szaflarski et al., 2018||treatment-resistant epilepsy||20-30mg/kg body weight||
|48 weeks||CBD reduced bi-monthly seizure frequency (144.4 > 46.7) and seizure severity (80.7 > 34.6).|
|Thile et al., 2019||Lennox-Gastaut Syndrome||20mg/kg body weight||366||48 weeks||48% to 57% reduction in monthly seizure frequncy. 88% of patients/caregivers reported an improvement in the patient's overall condition.|
|Wheless et al., 2019||pediatric treatment-resistant epilepsy||10-40mg/kg body weight||61||9 days||Interaction with clobazam, however CBD generally well tolerated|
|Szaflarski et al., 2019||treatment-refractory epilepsy||5 to 50 mg/kg/day||
|Increased CBD levels were associated with improvement in seizure frequency|
|Devinsky et al., 2018||CDKL5 deficiency disorder and Aicardi, Doose, and Dup15q syndromes||55||48 weeks||Convulsive seizure frequency for all patients taking CBD decreased from baseline to week 12 and 48.|
|Szaflarski et al., 2018||treatment-resistant epilepsies||25mg/kg body weight||607||96 weeks||CBD reduced median monthly convulsive seizures by 51% and total seizures by 48% at 12 weeks. 52% patients had >50% reduction in convulsive seizures. 31% patients had >75% reduction, and 11% had 100% reduction.|
|Devinsky et al., 2016||treatment-resistant epilepsy||25-50mg/kg body weight||214||12 weeks||36.5% reduction in monthly motor seizures|
CBD and Pain
CBD pushes a lot of buttons in the human body. It’s what’s known as a pleiotropic molecule - it has multiple effects all at once. This is how it’s able to have a powerful effect on the perception of pain.
There are a number of pathways by which pain can be communicated, which involve the immune and nervous systems. Often pharmaceutical solutions to alleviate pain focus on a single pathway (opioid receptors), which can be effective but also have disastrous consequences. Just stimulating opioid receptors to manage pain can trigger addiction and lead to dependence.
CBD on the other hand works on pain in a more holistic way. It binds to several receptors, and/or modifies the sensitivity of receptors to other messengers that control pain throughout the nervous and immune system.
- CBD is a positive allosteric modulator of α1 and α3 subunits of Glycine receptors (Morales, Hurst and Reggio, 2017), which are involved in the perception of neuropathic and inflammatory pain. (*)
- CBD is a positive allosteric modulator of two specific subtypes of opioid receptor (mu (μ) and delta (δ)) receptors. (*)
- CBD is a positive allosteric modulator of GABAa receptors, which means they are more sensitive to the pain relieving signals sent by the GABA neurotransmitter. (*)
- CBD also activates TRPV receptors, mainly types 1,2 and 3. These receptors play an additional role in reducing pain (*)
CBD also modulates the endocannabinoid system - a central regulator of pain.
- CBD increases cannabinoid receptor (CB1) activation. This receptor is found throughout the nervous system in circuits that control perception of pain. When activated, it reduces the ‘volume’ of pain signals from other neurotransmitters.
- CB1 activation also reduces the release of inflammatory pain messengers from mast cells within the immune system. This reduces inflammatory pain.
- CBD increases CB2 activation. CB2 is found on most types of immune cell, and when activated reduces inflammatory pain messengers (cytokines).
One clinical trial with CBD at doses of 2.5-120mg/day showed that it was able to reduce neuropathic pain in patients with MS and spinal cord injury (*),
The oral spray Sativex contains a 1:1 ratio of the psychoactive cannabinoid THC and non-psychoactive CBD (delivers 2.7 mg THC and 2.5 mg CBD per actuation) has been effective for managing neuropathic pain in MS (*), (*), (*) but is not prescribed for this purpose.
Studies have shown that THC, one of the active ingredients in Sativex, is effective for managing neuropathic pain in HIV, trauma, diabetes, chemotherapy, and other conditions (*).
The evidence suggests a more powerful effect when CBD is combined with THC. However, for legal and accessibility reasons, CBD may still help.
A survey of over 2000 regular CBD users found that pain was amongst the most common use for CBD (*). Up to 65% of those surveyed said CBD worked moderately to very well by itself, and 30% said it worked well in combination with other medication.
Topical CBD has also shown some promising effects on the perception of pain. A CBD gel was applied twice a day in patients with myofascial pain for 14 days, which significantly reduced pain scores compared to placebo (*).
After 4 weeks of using topical CBD, patients with symptomatic peripheral neuropathy had a significant reduction in intense pain, sharp pain, cold and itchy sensations compared to those not using CBD (*).
CBD and Psychosis
Psychosis can crop up in tandem with other neurological diseases such as Alzhiemers, Parkinsons and Schizophrenia.
Patients with these conditions have been reported to have abnormal levels of endocannabinoids in their blood, brains and spinal fluids when compared to healthy, aged matched control subjects ®. This is thought to be an underlying mechanism contributing to psychosis.
Neurological function (mood, memory, conscious awareness) depends on healthy endocannabinoid system function. Without balanced endocannabinoid signalling, neurones can miscommunicate and also start to degrade structurally.
Such is the case in psychosis, where nutritional, emotional and environmental factors contribute to endocannabinoid system imbalance over time, leading to the breakdown of healthy brain function.
CBD, as a structurally and functionally similar ‘sibling’ to endocannabinoids is able to make up for excesses or deficiencies in levels of endocannabinoids in the brain. The result is improved neurological function overall, through restoring balance to the endocannabinoid system as a whole. CBD improves the way neurons in the brain ‘talk’ to each other, as well as keeping them structurally healthy and responsive.
Two randomised, double blinded clinical trials have shown that CBD improved symptoms of psychosis in Schizophrenia.
After 6 weeks patients receiving CBD (alongside antipsychotic medication) had significantly better psychosis symptom scores when compared to placebo (n=88). Those receiving CBD were also deemed as less unwell, as well as showing a trend towards improved cognitive and overall functioning compared to placebo (*).
After 4 weeks, CBD was able to reduce symptoms of psychosis in schizophrenic patients just as effectively as the antipsychotic medication amisulpride (n=42). Levels of the endocannabinoid anandamide were also shown to improve after CBD treatment, and were associated with the improvements in symptoms of psychosis. CBD was also shown to have significantly less side effects than amisulpride, making it an attractive alternative option (*).
Two open label clinical trials also showed an improvement in psychosis with CBD.
6 parkinsons patients with psychosis were given CBD in addition to their usual therapy for 4 weeks. At the end of the study, psychotic symptoms evaluated by the Parkinson Psychosis Questionnaire had significantly improved. CBD also improved scores of the Unified Parkinson's Disease Rating Scale, indicating an overall improvement of their condition (*).
Prolonged Cannabis use is associated with psychotic-like experiences in some users. 20 frequent cannabis users were given CBD daily for 10 weeks. At the end of the study, they reported significantly fewer depressive and psychotic-like symptoms compared to when the study started. They also showed improvements in attentional switching, verbal learning, and memory. CBD levels in the blood were associated with improvements in attentional control and psychological symptoms (*).
CBD and Huntington’s
Huntington’s is a progressive neurodegenerative disorder that is inherited genetically. Mutations in the huntingtin gene (HTT) eventually lead to the breakdown of neurons within the brain, resulting in progressive loss of mental abilities, cognition and mood. Characteristic of later stage Huntington’s is a loss of motor coordination, with shaking (dystonia) being one of the hallmarks of the disease.
Although CBD can’t change someones genetic code, it may have effects that could alleviate the downstream consequences of the mutant gene.
Studies in rodents have shown that CBD and a broad spectrum of other cannabinoids not only reduce symptoms associated with Huntington’s, but also slows disease progression (*). CBD and other cannabinoids had a neuroprotective effect - they prevented the degradation of neurons, which counteracts the degenerative effect of the mutant gene.
No studies have been conducted on the use of CBD in humans and the progression of Huntington’s disease over a long period of time. So any indication that CBD could delay the disease's development in humans is unknown.
However, there are studies which show that CBD may be beneficial for managing the symptoms of Huntington’s, when the disease has already partially developed.
In a double blind crossover study, 10 mg/kg CBD/day for 6 weeks had no significant or clinically important effects in 15 Huntington’s patients (*). Although, additional trials with larger sample sizes are needed to clarify a lack of effect.
In an open label study, Incremental doses of CBD (100 to 600 mg/day) over 6 weeks improved dystonia by 20-50% in a dose-related manor in 5 patients (*). Despite anti dystonic effects in 3 patients, CBD aggravated hypokinesia and resting tremor in 2 Parkinson's patients.
What’s important to note in these studies is that they are very small, and were using an isolated form of CBD. As seen in the rodent study, the researchers used a cocktail of broad spectrum cannabinoids not limited to just CBD. Whole plant or broad spectrum CBD extracts have been shown to be clinically far superior to isolated CBD (*).
CBD and Type II Diabetes
There’s been a lot of research surrounding the use of cannabinoids for the control of metabolism. Most of this research has been in animals, and looks at how cannabinoids like CBD can alter the way sugars and fats are used as energy, and how they are stored as body fat.
Not just that, but the powerful antioxidant and anti-inflammatory properties of cannabinoids like CBD are also receiving a lot of attention for their ability to slow the progression of type II diabetes.
A large body of research has also shown that people with type II diabetes have severe imbalances in their levels of naturally produced cannabinoids (endocannabinoids) (*). These are at the very core of ensuring metabolism and blood sugar regulation is running smoothly. So supplementing externally sourced cannabinoids like CBD can help restore such imbalances.
A few population based studies have shown that cannabis users have a lower risk of developing type II diabetes (*). They also show that cannabis users have a lower body mass index and better blood sugar and lipid measures compared to non-cannabis users (*).
However, there is only one clinical trial that has actually looked at the effects of CBD specifically on markers of diabetes in people currently suffering from the disease.
200mg CBD / day did not have any effect on markers of inflammation, blood lipids, or blood glucose after 13 weeks in 62 type 2 diabetes patients compared to placebo. However, CBD significantly decreased resistin (-898 pg/ml) and increased glucose-dependent insulinotropic peptide (21.9 pg/ml) compared to placebo (*).
These hint at a slight improvement in metabolic control, but the dose of CBD used was so low throughout the study that you wouldn’t expect much benefit. Also, the type of CBD used has been shown to be less effective than whole-plant CBD (*).
Similar studies using whole-plant CBD, at higher doses will most likely show us what the population studies show - a benefit for diabetes.
CBD and Anxiety
Arguably the most popular use for CBD is for anxiety - an antidote to the stresses and woes of the 21st century. It’s no mystery why it’s become the chillout substance of choice.
A couple of cross-sectional (surveys) studies support the anecdotes of people that use CBD oil for anxiety. The two studies found that anxiety was one of the top 3 reasons that people were using CBD oil, alongside depression and pain.
CBD is considered non-psychoactive, yet can shift a person’s mood from a state of distress into a state of calm. Although not fully psychoactive, there is clearly a subtle yet clinically meaningful effect on mood.
When we look at the mechanisms of action relating to CBD, we discover just why it is such a powerful anxiolytic (anti-anxiety) and antidepressant.
CBD works in the brain and nervous system just like anti-anxiety and antidepressant drugs do.
SSRI’s (selective serotonin reuptake inhibitors) increase the amount of available serotonin by preventing its degradation, which stabilizes and boosts mood. Serotonin is an important neurotransmitter for feelings of confidence, happiness and safety.
CBD does something similar to SSRI’s, by increasing the brain’s sensitivity to available serotonin, which also boosts mood.
Benzodiazepines, like valium and xanax work on another neurotransmitter system called GABA which governs feelings of relaxation and calmness. They enhance GABA signalling to reduce feelings of anxiety in the short term, but have disastrous consequences when used long term and can foster extreme dependence and mood instability.
Again, CBD does something similar here, but supports as opposed to hijacks GABA signalling. CBD increases the brain’s sensitivity to GABA’s calming and relaxing instructions, helping to relieve anxiety and chill out.
If already taking antidepressants, be cautious of also using CBD. Check CBD interactions with medications, and work with your doctor before deciding to change anything around medications.
Another way CBD prevents anxiety is through its effect on the bodies internal cannabinoid system. The body already produces its own natural ‘feel good’ cannabinoids, one of which is called Anandamide. But, some people may be running low on these and are subject to a depressed mood and anxiety. CBD boosts levels of Anandamide in the brain, which then tells the rest of the brain and its happy neurochemicals to perk up, fostering a universal uplift in mood.
CBD also works on hormonal pathways which signal for stress responses. The HPA axis is a hormonal highway which effectively acts as the alarm system in response to stress. Chronic stress can keep alarm bells ringing, and cause the constant release of stress hormones within the HPA axis - cortisol is one of them. CBD actually acts to damped down the alarm bells, and resolve stress responses, by changing cortisol release (*).
There are a few other ways biochemically that CBD reduces anxiety, but I won’t bore you with the details. But I will talk about some studies whereby CBD has been shown to have an impact on anxiety in humans.
Most studies relating to anxiety have used the same methods to assess its impact. They used simulated public speaking tests to create an anxiety inducing phenomenon, and saw how the responses in those that received CBD and those that didn’t differed.
3 studies using doses of CBD ranging from 150mg - 600mg found that those receiving CBD during public speaking tests had reduced scores of anxiety, discomfort and cognitive impairment compared to those that didn’t (*), (*), (*). This was especially true for people that had social anxiety disorder (SAD).
As we’ve discussed, beneath these changes are the neurochemical mechanisms that change brain chemistry. One other study gave CBD at a dose of 400mg and conducted neuroimaging (brain scans) as well as measuring scores of anxiety in participants. Those receiving CBD had significantly reduced anxiety, as well as a reduction in Anandamide uptake in emotional processing centres of the brain (limbic and paralimbic brain areas) compared to those that didn’t receive CBD (*).
Anxiety relief is an almost universal effect of CBD, and has been documented in a few case studies which were looking at other conditions. Anxiety can occur as a co-morbid condition with other conditions, such as cancer, neurological diseases such as parkinsons and neuropsychiatric conditions such as depression.
In one case study at a psychiatric clinic, 25 psychiatric patients with sleep disorders taking 25 - 75mg CBD /day improved subjective sleep scores by 28% after 3 months. They also had significantly improved measures of anxiety, which may explain the improvement in sleep quality (*).
Another case study found that levels of anxiety were much improved in one individual with PTSD taking 18-25mg CBD (likely whole plant extract). Their sleep also improved (*).
CBD and Multiple Sclerosis
MS is an auto-immune condition where the immune system is responsible for the degradation of the protective layer (myelin sheath) surrounding neurons within the brain and nervous system. This leads to a wide array of mental, physical and emotional symptoms, as the nervous systems ability to communicate properly is impaired.
Cannabinoids like CBD are especially helpful for auto-immune conditions, because they are immunosuppressive, and can calm an overactive immune system down. This helps reduce the self-destructive activity of the immune system on various bodily tissues, such as nervous tissue as is seen in MS.
They can also help partially restore nervous system function, even when there has been interruption to propper nervous signalling because of neuron destruction. CBD and other cannabinoids help restore neuronal function by encouraging their regrowth, and by helping restore the co-ordination of messages sent via the nervous system that correspond to EG pain perception, mood and movement.
Most research in Multiple sclerosis has used full blown cannabis extracts, containing both THC and CBD, with some promising results. Sativex, a pharmaceutical THC:CBD spray (delivers 2.7 mg THC and 2.5 mg CBD per spray) has shown to reduce neuropathic pain in Multiple Sclerosis as well as symptoms of spasticity (*), (*), (*).
A couple of studies have also shown that CBD alone (2.5 mg CBD per spray) has an effective pain killing effect, greater than receiving a placebo. But, they also showed that the pain killing effect of CBD is greater when combined with THC (*), (*).
CBD and Hypertension
High blood pressure, or hypertension can often occur with stress, or as a result of a stressful way of living.
CBD has a pretty significant interaction with the cardiovascular system, through its interaction with the endocannabinoid system.
It can help control blood pressure in two ways:
- CBD can dilate blood vessels to reduce blood pressure
- CBD can also control the nervous system and by extension influence heart rate, which may change blood pressure
There are many other ways which CBD may support heart health in general, but they have only been studied in animal/mechanistic studies so far.
In a crossover RCT, a single dose of CBD at 600mg reduced blood pressure (–5 mmHg), increased heart rate (+10 bpm) and decreased stroke volume (–13 ml) in response to physiological and psychological stressors (*).
This is exciting data, because it suggests that CBD may be helpful in combating the damaging effects that stress has on blood pressure.
CBD and Inflammatory Bowel Disease (IBD)
As the name suggests, inflammation is a key driver of disease progression in IBD. As inflammation is unrelenting, it continues to damage the intestinal lining in distinct ways between ulcerative colitis (UC) and Crohns. Behind this inflammation is an immune system that’s confused, as it attacks the body and its tissues - specifically the intestinal lining.
This is an autoimmune reaction, where the immune system specifically recognises intestinal tissue as foreign and attempts to destroy it.
The inflammation in the gut also propagates a basket of other symptoms, including diarrhea, fatigue, foggy thinking and problems with mood - depression and anxiety. Weight loss is also common due to inefficiency absorbing nutrients from food.
So far as interventions go for IBD, it doesn’t get much better than cannabinoids, including CBD. Whilst the root causes of inflammation need to be addressed, CBD can help rebalance the gut ecosystem whilst root causes are being corrected.
One way CBD can help is by suppressing the immune system, specifically T cells or TH1/17 which are behind excessive levels of inflammation. The immunosuppressive effects of CBD may not only spare the gut against further damage, but also reduce the impact of inflammation on diarrhea, energy levels and mood.
CBD also has anti-depressant and anti-anxiety effects within the brain through serotonin signalling, so may work to bypass the negative impact the gut has on the brain and mood.
Research in animals argues an encouraging case for CBD in IBD, but sadly the studies in humans have yet to be conducted in a way which demonstrates CBD’s efficacy.
A randomised controlled trial failed to show any improvements in Crohn’s disease activity index relative to placebo with 20mg CBD / day after 8 weeks. There were also no differences in inflammatory markers (*).
The key thing to mention here is that this study used CBD isolate, and at doses which would have little to no effect at all. Bear in mind that other studies have had to use at least 300-1200mg CBD isolate / day to demonstrate an effect on diseases and conditions. The dose used in this study was only 20mg CBD/day. More robust studies are needed with whole plant CBD, at higher doses and with more than 19 participants to be well powered enough to show an effect for Crohn’s.
Another randomised controlled trial found that 250mg / day of whole plant CBD for 10 weeks significantly improved scores (of remission) in ulcerative colitis patients. The patients also said their perceived quality of life had improved significantly compared to those not receiving CBD (*).
However, this study didn’t measure markers of inflammation, which will be interesting to see from future studies.
CBD and Addiction
One thing you would not expect from CBD is its effect on addiction. Cannabis has been pushed as an addictive substance for decades, and whilst THC can be addictive for some people, it isn’t CBD.
THC and CBD are what’s known as major cannabinoids - they make up the majority of the plants cannabinoid content compared to the other ‘minor’ cannabinoids.
But, modern strains of cannabis have been bred for high THC and lack the CBD counterpart. CBD is needed for a balanced effect on brain chemistry, and impacts how rewarding THC is and how likely you are to become addicted to it.
With that said, let’s take a look at how CBD can actually buffer the addictive qualities of not only THC, but also other drugs that trigger a sense of reward, and therefore can become addictive.
THC and other drugs release a rewarding chemical called dopamine. This produces a sense of fulfilment, satisfaction and reward, which can leave people wanting more. Unless someone has access to a rich source of dopamine through hobbies, social activities, sports, music or work, they may seek reward from substances.
CBD can actually help people recovering from addiction, by blunting the rewarding qualities of certain drugs. It can also stabilize dopamine levels through the ECS as well as working directly on dopamine receptors, which means it may reduce drug cravings, and susceptibility to relapse and further addiction.
There are a few exciting studies which support what I have said above.
A randomised controlled trial found that smokers who received CBD reduced their cigarette consumption by up to 40% after 1 week, compared to those that didn’t get CBD (*).
A population study found that smoking high CBD:THC cannabis was associated with lower dependence scores compared to high THC:CBD cannabis in 94 regular smokers (*).
In a clinical trial, 41 cannabis users were given 200mg CBD/day for 10 weeks. At the end of the study, participants reported significantly fewer depressive and psychotic-like symptoms had improvements in attentional switching, verbal learning, and memory (*). Having these symptoms under control is helpful for reducing cannabis dependence.
A randomised controlled trial (pilot) showed that CBD given for 3 days to Heroin users in remission significantly reduced their craving and anxiety when they were given a drug cue. These effects lasted for up to a week after the initial 3 days of CBD use (*).
A 27-y-old man with bipolar disorder and a daily addiction to cannabis use took CBD for ~ 6 months at a dose of 18-24mg/day. With use of the CBD oil, the patient reported being less anxious, as well as settling into a regular pattern of sleep. He also indicated that he had not used any cannabis since starting the CBD oil. With the decrease in the dosage to 18 mg, the patient was able to maintain his nonuse of cannabis (*).
CBD, Cannabis Dependence & Side Effects
The ironic thing about CBD is that it may actually help cannabis users cut down or even discontinue their cannabis use. Also, for existing cannabis users who experience side effects, such as paranoia, anxiety, appetite stimulation and poor sleep after prolonged use, CBD may be able to offset some of these too.
When it comes to addiction, CBD and THC have opposing “yin/yang” effects on reward processing and addiction-related behaviours. In contrast to THC (which is rewarding and promotes drug seeking), CBD has low abuse potential and actually discourages drug seeking (*).
THC causes a rush of reward by triggering the release of dopamine, which is a neurotransmitter which signals for motivation and reward. Because it is a feel good brain chemical, it can leave individuals wanting more, leading to addictive tendencies.
However CBD does the opposite of THC when it comes to reward. It can actually block the overly stimulating actions of THC in the brain (*), by preventing THC from overly stimulating the CB1 receptor (which is where dopamine release is triggered from). This means CBD can be used to prevent addictive behaviours around cannabis use (and potentially) other drugs too.
So for cannabis users who are exposing their brains to high amounts of THC, introducing CBD may actually be offsetting the overly rewarding, potentially addictive properties of THC.
It’s worth mentioning that many strains of modern cannabis are almost exclusively THC heavy, with very little to no CBD. Most Cannabis has been selectively bred for the high that it produces from THC, whereas little attention was paid to the benefits of the other cannabinoids including CBD. This may be one of the factors that drives cannabis dependence.
Studies on CBD and cannabis dependence
A repeated measures study in 94 regular smokers found that those using high CBD:THC cannabis had lower dependence scores compared to those using high THC:CBD cannabis (*).
A 19 year old female with cannabis dependence, who also experienced withdrawal when trying to quit cannabis was given CBD. After having been given CBD for 11 days, she experienced less (marijuana) withdrawal symptoms, anxiety and depression. After 6 months, her use of cannabis had been reduced from 7 days a week to once or twice a week (*).
CBD and Cannabis Side Effects
In the same way CBD can curb the addictive qualities of THC, it can also reduce some of the less desirable side effects from it too.
Some of the common side effects with THC are paranoia, memory loss, anxiety, depression, appetite stimulating effects and loss of motivation.
These can be an issue for THC users who want to get the therapeutic benefits from it, but without the undesirable side effects. So this is where CBD comes in.
One RCT found that healthy subjects who were given CBD before taking THC had less occurrence of psychotic symptoms (paranoia) in addition to memory issues compared to those just given THC alone (*).
An open label study, 20 regular cannabis users took CBD daily for 10 weeks and found that after having taken CBD, compared to when they started, the users reported significantly fewer depressive and psychotic-like symptoms and had improvements in attentional switching, verbal learning, and memory (*).
One observational study found that users of high CBD:THC strains of cannabis showed less interest in food cues than users of high THC:CBD strains (*). This indicates less of a ‘munchies’ effect of THC when there is more CBD present.
CBD and PTSD
PTSD is a type of anxiety disorder, which is associated with the recall of traumatic memories and an inability to resolve stress. Nightmares and disrupted sleep are also common problems with PTSD.
You may be thinking already, since CBD can help with sleep and anxiety, then it may be the perfect for PTSD.
The truth is though, there just aren’t many robust studies out yet to confirm what we already know about CBD.
Everything else seems to add up though. If we take a look at the ECS of people with PTSD, we see it's under-active. Individuals exposed to the World Trade Centre attack who had developed PTSD, had a reduced level of the endocannabinoid 2-AG compared to those without PTSD (*). Other people with PTSD and a history of trauma also had reduced levels of the other endocannabinoid, Anandamide (*).
It's no wonder they have trouble sleeping, nightmares, anxiety and find it difficult to escape stress.
These are all symptoms that come with a low functioning ECS. Adulthood trauma has been shown to reduce the activity of the ECS (*). It makes sense that CBD could pitch in here, since it can increase the activity of the ECS, by increasing anandamide (*).
Now, I’m not going to suggest that CBD can ‘cure’ PTSD. The fact of the matter is each individual with PTSD has experienced a traumatic emotional event that has manifested in a biochemical change in their ECS. That doesn’t mean that propping up the ECS with CBD will get rid of the problem, it potentially offers an attractive means to help manage it.
Truly treating PTSD may involve some sort of special psychotherapy that addresses the root cause of the issue - the traumatic memory and the emotions attached to it.
Studies in PTSD
In a case series (low quality evidence), CBD has been shown to reduce the PCL-5 score in PTSD patients by 28% (rating of PTSD symptom severity) after 8 weeks of use. Although only 11 people were monitored in this case series, this still provides encouraging data. What’s also interesting is that a third (36%) of the patients had improvements with their nightmares, and 72% reported improved sleep quality (*).
CBD is known to improve sleep quality and alter the time spent in deep and restorative phases of sleep (*), so it's encouraging to see that data replicated here, in PTSD patients.
CBD, Autism & ADHD
Although it's not psychoactive, CBD has subtle mood altering effects which make it useful for various conditions such as depression and anxiety.
Another use case for CBD is for attention (ADHD), which is a common comorbidity with things like depression, anxiety and Autism (ASD). Most of the studies are looking at ADHD with relation to ASD.
Autism is typically characterised by intellectual disabilities, behaviour abnormalities and issues with social communication. However on top of that are also issues with attention, sleep, mood and epilepsy.
CBD is a pleiotropic molecule with many different targets pharmacologically, which makes it a potentially useful compound when dealing with multiple symptoms associated with ASD.
I believe this is why studies in ASD have shown diverse outcomes when looking at the broad range of ASD symptoms.
One study found that in children using whole plant CBD (20:1 CBD:THC), there was a 67% improvement in rage attacks and self injury. However, it worsened these symptoms in 8% of children. In 68% of children, ADHD symptoms improved, 29% had no change and 3% had worsened ADHD. In 71% of children sleep improved, 47% had improved anxiety in 23% it worsened (*).
Its possible CBD exacerbates ECS imbalances in the children that had worsening symptoms. Trying alternative doses and/or cannabinoid ratios may help improve the other childrens symptoms.
In another study using CBD:THC combinations in ratios of 20:1 and 6:1, there was a significant improvement in 61% of children’s behaviour problems, in addition to a 47% improvement in anxiety. For disruptive behaviour, there was a 29 and 33% improvement at the end of the study compared to the start (*).
After 6-9 months of treatment with a CBD extract (CBD to THC ratio of 75/1) in ASD patients, an observational study showed a significant improvement in symptom categories including ADHD and sleep after using doses on average around 450mg CBD/day (*).
There is no research with CBD exclusively with relation to ADHD that is not related to ASD, however one study found an improvement in ADHD symptoms in adults when using THC:CBD in a 1:1 ratio (*).
CBD and Parkinsons
Parkinsons disease is characterized mostly by the loss of motor control that happens as a result of the gradual loss of dopamine producing neurons.
As a result of the loss of neurons, the brain is unable to produce enough dopamine to maintain control of limbs and balance, which results in tremors, but also sleep, anxiety, depression, fatigue and issues with cognition, mood regulation and irritability.
Despite the loss of neurons, CBD can help boost levels of dopamine in remaining neurons, in addition to helping preserve the structure and function of existing neurons by acting as a neuroprotectant.
CBD also lends benefit to the mood and sleep disorders experienced in Parkinsons, by attempting to restore equilibrium within the Endocannabinoid System and nervous system.
CBD in a flexible dose (started with an oral dose of 150 mg/day) for 4 weeks significantly decreased psychotic symptoms and ratings of Parkinsons Disease severity in 6 patients, and was well tolerated. The only caveat here is a lack of control group (*).
4 Parkinsons patients with REM sleep disorder were treated with 75 - 300mg / day CBD for 6 weeks. 3/4 patients completely eliminated frequency symptoms (1-7 x per week > 0 x per week). 1 Patient still experienced symptoms (1 x / week), but still improved from 4 x / week (*).
An RCT found 300mg CBD for 6 weeks to significantly improve quality of life scores compared to placebo in 21 patients despite no differences in plasma BDNF and general symptom scores (*).