Meta-Analysis: Studies on Cannabis, Stress, and Inflammation — Leafwell

Summary: The ECS plays an important role in stress and inflammation, which are a part of almost every single health problem. Targeting the ECS with medical cannabis could potentially help treat a number of symptoms associated with stress due to its immunomodulatory effects.

Stress leads to inflammation. Inflammation plays a key role in the etiology of almost all health problems, and there’s even the idea that inflammation is a unifying theory of disease. Stress also alters memory functions, reward mechanisms, immune function, metabolism, and susceptibility to diseases.

Now, not all stress and inflammation is bad, as it’s a process that helps us fight disease, heal from injuries and decide whether to “fight or flight.” However, if the stress and inflammation become chronic, it can become extremely detrimental to human health. Constant stress can lead to tissue breakdown and impair the immune system. Other common indicators of stress include aches and pains, increased heart rate and hypertension (including chest pain), exhaustion, headaches, dizziness, muscle tension, stomach and digestive problems, sleep problems, and sexual dysfunction.

Many people ask, “ Why does medical cannabis seem to help with so many conditions? “ The simple answer may be, “Because it beats stress.” The longer and more detailed answer could be:

The endocannabinoid system (ECS) is fundamentally linked to homeostasis (keeping the human body’s physiological processes in balance), inflammation and immune response. When you suffer from a health problem, your ECS is dysregulated, and inflammation is the result. Medical cannabis and cannabinoid-based medications could help re-regulate the ECS, and stem inflammation.

Indeed, endocannabinoids, of which anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are the main two, are produced on-demand in response to stress, and generally function to mediate stress response. You could say that when you are stressed, there’s a sort of tug-of-war going on between your ECS and your stress response system.

Your ECS is trying to reduce inflammation, whereas cortisol — the body’s main stress hormone and “ alarm system” — is trying to ramp up the release of inflammatory cytokines (“small soluble proteins that mediate communication among immune and non-immune cells”). However, this is a simplistic explanation, as the ECS is also involved in activating stress response. In this sense, you could argue that the ECS is both a player and a referee in this game of tug of war.

Again, stress is not always bad, but if the cortisol wins this tug-of-war too often because of constant stress, it can cause chronic inflammation that leads to other health problems. With the aid of cannabis-based medications, you can allow your ECS to win on the occasions you need it to (e.g. if you’re suffering from a migraine, unnecessarily anxious or going through a bout of insomnia), and potentially stem the tide of stress and inflammation.

What Sort of Health Problems Can Stress Cause?

As noted above, stress and inflammation is implicated in the development of many conditions. There are, however, some conditions that have a particularly strong connection with stress. These include:

• Headaches and Migraines: stress is “the factor listed most often by migraine sufferers as a trigger for their attacks, but in addition there is evidence that stress can help initiate migraine in those predisposed to the disorder, and may also contribute to migraine chronification.” So, migraines may not only be a trigger, but also potentially a cause, and can also increase the frequency and chronicity of migraines. Stress-induced headaches may be referred to as “tension type headaches (TTH).” Stress-related headaches and migraines are also associated with a serotonin imbalance.
• Arthritis: stress is linked to an increase of inflammatory arthritis. Stress, depression and insomnia are also associated with arthritis, and treating these may help manage arthritis.
• Gastrointestinal (GI) problems (e.g. IBS, gastroesophageal reflux disease (GERD),chronic heartburn): stress can reshape gut bacteria composition, which can alter eating behavior and mood.

Could Medical Cannabis Help Treat and Beat Stress?

The ECS is certainly involved in the mediation of stress, and is involved in both activating and terminating the HPA axis response to both acute and chronic stress. Brain regions associated with stress response also have a high concentration of CB1 receptors. Modulating CB1 receptors may therefore also alter our response to stress. There is some research suggesting that consuming low doses of tetrahydrocannabinol (THC) — a partial agonist of CB1 receptors — can relieve stress, whereas consuming more does the opposite and prompts stress.

Cannabis use can alter multiple stress response systems, and long-term use may lead to significant changes in how stress response systems function. One study suggests that long-term cannabis use (1-year or longer) may have an adverse effect on the stress response system, but variables and vulnerability factors such as early life adversity, sex and pregnancy are not fully taken into account.

The same study also references several studies showing that chronic cannabis use may be associated with blunted stress response. Whilst this may seem negative, for those with conditions like PTSD and anxiety where stress and hypervigilance is more regular and constant, this could potentially be of benefit, and may even help in recovering from PTSD.

In one of the first scientific guidelines on using cannabis to treat stress, anxiety and depression, Washington State University (WSU) scientists found that:

“[O]ne puff of cannabis high in CBD and low in THC was optimal for reducing symptoms of depression, two puffs of any type of cannabis was sufficient to reduce symptoms of anxiety, while 10 or more puffs of cannabis high in CBD and high in THC produced the largest reductions in stress.”

Let’s take a brief look at why medical cannabis could help treat and beat stress in the conditions mentioned above.

Anxiety

• A 2010 study found that cannabidiol (CBD) oil reduced anxiety symptoms in people with social anxiety disorder. Brain scans revealed an increase in blood flow to regions in the brain linked with feelings of anxiety.
• Low doses of THC may help induce relaxation, which in turn may help ease anxiety symptoms.
• Cannabis contains a vast array of terpenes (e.g. pinene, limonene, beta-caryophyllene) that may have anxiolytic (anti-anxiety) and antidepressant effects.

Depression

• Although there are differences between anxiety and depression, the two conditions often overlap, and they may have the same basic underlying cause. Many of the reasons why cannabis may help with anxiety may apply to depression, too (i.e. improve mood, aid sleep). However, different dosing regimens may be needed for anxiety-only, depression-only and comorbid anxiety-depression groups.
• CBD is an inverse agonist of the serotonin receptor, 5HT1A. Antidepressants also target this receptor, but CBD may be more tolerable and have fewer adverse side-effects (e.g. insomnia, mood swings, agitation, and sexual dysfunction) by comparison.

PTSD

• Sometimes even drugs that have no proven efficacy for PTSD (e.g. benzodiazepines, antipsychotics) are still prescribed. In fact, such prescription drugs may make PTSD worse if used in the long-term. Medical cannabis may help replace these substances, and cannabinoids like cannabinol (CBN) may have similar sedative effects to benzodiazepines, but with far fewer negative side-effects. Medical cannabis may also help reduce benzodiazepine use.
• Cannabis may help reduce activity in the amygdala — the part of the brain associated with fear responses to threats. Low doses of THC showed measurable signs of reduced fear and anxiety.
• Cannabis, and THC in particular, may help extinguish or help reassess traumatic memories.

Insomnia

• Endocannabinoids play a significant role in the regulation of the sleep-wake cycle — phytocannabinoids may help restore a disturbed sleep-wake cycle in insomniacs.
• Cannabis may reduce the amount of time it takes for a person to get to sleep.
• Cannabis contains several terpenes that may help induce sleep and relaxation, such as linalool, myrcene and ocimene.

Headaches and Migraines

• THC may reduce serotonin release, which can possibly help reduce the intensity of headaches and migraines.
• Nausea and vomiting are potential side-effects of migraines, and cannabinoids like THC and CBD may help prevent these side-effects.
• Migraines are hard-to-treat, and some of the stronger medications have negative side-effects in comparison to medical cannabis.
• “In migraines, current theory suggests that the CB system mitigates migraine through several pathways (glutamine, inflammatory, opiate, and serotonin) both centrally and peripherally [4]. Anandamide (AEA) potentiates 5-HT1A and inhibits 5-HT2A receptors supporting therapeutic efficacy in acute and preventive migraine treatment; it is active in the periaqueductal gray matter, a migraine generator. Cannabinoids also demonstrate dopamine-blocking and anti-inflammatory effects [5]. Furthermore, cannabinoids may have a specific prophylactic effect in migraines due to their ability to inhibit platelet serotonin release and peripheral vasoconstrictor effect [6]. In addition, CB1 receptors reduce nociperception via a serotonin-mediated pathway, whereas CB2 receptors act to produce analgesia without developing tolerance or side effects [4].” ‘Medical Cannabis, Headaches, and Migraines: A Review of the Current Literature’

Heart Disease

• CBD may help protect the heart from further damage, meaning the cannabinoid could be “cardioprotective“.
• For those who cannot tolerate blood-thinning medications such as warfarin or aspirin, CBD may be an alternative.
• Using cannabis can increase blood pressure in the short term, but potentially decrease it in the long-term, possibly helping to alleviate hypertension.

Asthma

• CBD may help as an antispasmodic, preventing the muscles in the lungs from contracting during an asthma attack.
• CBD reduces airway inflammation and fibrosis in experimental allergic asthma.
• Targeting CB1 and CB2 receptors may present a “novel preventative therapeutic strategy in asthmatic patients” — both CB1 and CB2 receptors help protect the lungs.
• Some cannabis terpenes and cannabinoids are bronchodilators, helping to open up the airway and/or aid breathing, such as THC, pinene, limonene, borneol and eucalyptol.

Arthritis

• Medical cannabis may help alleviate arthritic pain, which is associated with inflammatory, nociceptive and neuropathic pain.
• Insomnia, stress and mood issues are also linked to joint pain and arthritis. Helping treat insomnia, depression, and anxiety may help patients manage arthritic pain, and medical cannabis could be one potential treatment.
• CBD oil may act as an anti-inflammatory and lubricant for joints affected by arthritis.
• CBD could be an anti-arthritic that helps repair old bones.

Diabetes

• CBD and tetrahydrocannabivarin (THCV) could help regulate glucose levels and prevent insulin resistance.
• Cannabinoids like CBD may improve carbohydrate metabolism, helping control and maintain weight.
• Reducing levels of stress hormones could help insulin-producing cells in the pancreas function properly.

Obesity

• Using cannabis may increase metabolism, which can help burn more calories during periods of rest and activity.
• Reducing the level of stress hormones like cortisol could help reduce abdominal fat.
• People who are less stressed are more likely to have restful sleep. In turn, people who get adequate sleep are less likely to suffer from obesity.

GI Problems such as IBS and IBD

• Medical cannabis and cannabinoids like CBD may help modulate the immune system and prevent inflammation of the gut. Cannabis may possibly “reduce the increase of intestinal motility induced by inflammatory stimuli.”
• Reducing stress, anxiety and depression may help alleviate some of the pain and colon spasms associated with IBS and IBD.
• Altered gut flora, ECS tone and Vitamin D deficiency play a role in chronic inflammation and pain associated with IBS. Regulating the ECS could help return balance to the gut.

Alzheimer’s Disease

• THC could be particularly useful for removing beta-amyloid, the plaque-causing protein implicated in the development of Alzheimer’s and dementia.
• Terpenes such as limonene and pinene may help alleviate stress, “brain fog” and memory loss to some extent.
• CBD and cannabichromene (CBC) may have neuroprotective properties that could be of help in those with Alzheimer’s.

Autoimmune Disorders

• Evidence suggests that microRNAs (miRNAs, small non-coding RNA molecules that regulate gene expression in diverse biological processes) play a vital role in the regulation of immunological functions and the development of autoimmunity and autoimmune disease. There is crosstalk between the ECS, miRNA expression, inflammation and oxidative stress.
• Phytocannabinoids (phyto = plant, so cannabinoids from plants) may be useful in helping to modulate the immune system and preventing the release of pro-inflammatory cytokines.
• THC can “change critical molecules of epigenome called histones [a protein that provides structural support to a chromosome], leading to suppression of inflammation.“

Multiple sclerosis (MS)

• CBD may be neuroprotective, and may even counteract MS’s development because of CBD’s anti-inflammatory and antioxidative effects.
• THC and CBD could help manage neuropathic pain, muscle spasms and stiffness associated with MS.
• Medical cannabis could help reduce reliance on pharmaceuticals such as the antispasmodic, baclofen, and opioid-based painkillers.

Conclusion

The ECS is involved in the human body’s stress-response system and cannabis can modulate this system in several ways. There is a good body of scientific evidence to suggest that wise use of medical cannabis could help alleviate stress, reduce inflammation and help improve many conditions that stress plays a key role in.

More research is needed on what sort of dosing, cannabis constituents- cannabinoids, terpenes, flavonoids, etc.- may be useful in reducing stress-related conditions.

Note: the information in this article does not constitute medical advice.

Originally published at https://leafwell.com.