Ministry of Hemp

Ministry of Hemp

America's leading advocate for hemp

Tag: Endocannabinoid System

CBD For Bipolar Disorder: Can Cannabinoids Help Treat Bipolar Affective Disorder?

4.4 percent of adults are estimated to experience bipolar affective disorder. We took a look at research suggesting CBD and other cannabinoids could help.

We wanted to take a closer look at the science behind using CBD for bipolar affective disorder.

The National Mental Health Institute estimates 4.4 percent of adults in the United States will be given a diagnosis of bipolar affective disorder (BPAD) in their lifetime. Adults with BPAD experience the highest rate of impairment among psychiatric patients; an estimated 82.9 percent suffer from severe disablement.

Bipolar affective disorder and its variants can be treatment resistant, which may explain the high rate of disability. Anecdotal evidence, supported by preliminary studies, suggest that cannabinoids have the potential to improve the symptoms of BPAD in some individuals by regulating the endocannabinoid system.

WHAT IS BIPOLAR AFFECTIVE DISORDER?

Bipolar affective disorder is a mental illness that causes significant changes in mood, motivation and energy. A process known as cycling, which involves periods of euphoria (manic episodes) followed by hopelessness (depressive episodes), is a hallmark of the illness.

A man hands holding a white paper sheet with two faced head over a crowded street background.

Some preliminary research supports the use of CBD for bipolar affective disorder treatment.

There are four variants of bipolar affective disorder: bipolar I, bipolar II, cyclothymic disorder and bipolar spectrum disorders. The severity and frequency of symptoms are used to determine which variant is diagnosed. Bipolar I is the most severe form of the disease.

SYMPTOMS OF MANIC EPISODES

Manic episodes, sometimes referred to as mania, are characterized by exaggerated self-esteem, insomnia, racing thoughts and abnormal speech, inability to focus, and impulsive behaviours. True manic episodes only affect those diagnosed with bipolar I disorder. However, patients with other variants of BPAD experience hypomania, a less severe form of mania.

Although mania is considered to be the “high” stage of BPAD, it can have disastrous consequences. Many manic episodes result in hospitalization, psychotic symptoms or grave impairment (e.g., risky behaviour leading to legal trouble). Untreated manic episodes can develop into psychosis.

SYMPTOMS OF DEPRESSIVE EPISODES

Depressive episodes mimic a severe form of depression known as major depressive disorder. Symptoms can include feelings of sadness, emptiness, hopelessness, and loss of interest in activities. Additional traits of depressive episodes are changes in sleep patterns and appetite, trouble concentrating, feelings of worthlessness or guilt, and suicidal thoughts or attempts.

This cycle of bipolar disorder is the “low” point of the disease. Like mania, depressive episodes vary in severity depending on which variant of bipolar disorder is present. Patients with Bipolar I disorder may have what are known as mixed episodes, during which they show signs of both mania and depression.

CONVENTIONAL TREATMENTS OF BIPOLAR DISORDER

Prescription drugs used in conjunction with psychotherapy can help alleviate symptoms of BPAD in most patients. However, bipolar affective disorder can be treatment-resistant, making it difficult to manage in some people. Treatment-resistant BPAD is cause for concern, as up to 50 percent of individuals diagnosed will attempt suicide at least once in their lives.

Medications prescribed for BPAD include anticonvulsants, antimanic drugs and antidepressants. Use of antidepressants alone can lead to the onset of mania or rapid cycling. Mood stabilizers or anticonvulsants are often taken to negate these possible side effects.

The only pharmaceutical shown to have a consistent, positive effect on suicide rates in bipolar patients is lithium. However, newer research has shown there may be a possibility to control BPAD through manipulating the endocannabinoid (EC) system. These are the neurotransmitters responsible for binding cannabinoid proteins to receptors.

ENDOCANNABINOID SYSTEM DYSFUNCTION AND BPAD

The endocannabinoid system, discovered in the mid-1990s, is comprised of two receptors, CB1 and CB2. Cannabinoids, a type of compound found in both the human body and cannabis plants, bind to these receptors to alter brain function. Endocannabinoids are neurotransmitters produced naturally in the body, while phytocannabinoids are found in cannabis plants.

 

An illustration of neurons firing in a human head. Post-mortem studies of human brains of people with bipolar affective disorder found some abnormalities in how they process cannabinoids.

Post-mortem studies of human brains of people with bipolar affective disorder found some abnormalities in how they process cannabinoids.

Postmortem studies have found that brains of patients diagnosed with mental illness, including BPAD variants, show abnormalities in the endocannabinoid system. A similar study, conducted using brain slices from mice, showed dysfunctional CB2 receptors inhibited the release of serotonin, suggesting a healthy EC system helps to regulate mood.

An investigation of endocannabinoid gene variants in 83 patients with major depressive disorder (MDD), 134 with BPAD, and 117 healthy control participants found two marked differences in the patients afflicted with MDD and BPAD. Specifically, the CB1 receptor (CNR1) and fatty acid amide hydrolase (FAAH) genes of the ill participants were found to be abnormal when compared to the control group.

REGULATING THE EC SYSTEM WITH PHYTOCANNABINOIDS

Because of the distribution of endocannabinoid receptors throughout the brain, many of the areas they affect overlap with regions thought to be responsible for BPAD, along with other mental illnesses. Studies have shown patients with specific abnormalities in the CNR1 gene are at a higher risk of being resistant to pharmacological treatment, leaving them more vulnerable to the effects of bipolar affective disorder.

For these patients, phytocannabinoids could provide a way to manipulate the EC system and regulate the level of chemicals traditionally targeted by pharmacological medications. As always with hemp and cannabis research, these studies are still preliminary. More research will be needed to prove whether CBD and other cannabinoids can help treat bipolar affective disorder.

Anandamide and THC

Anandamide, called the bliss molecule, is naturally produced in the body and is similar in molecular structure to THC. Both anandamide and THC bind to CB1 receptors, altering areas of the brain responsible for memory, concentration, movement, perception, and pleasure.

FAAH genes are responsible for activating anandamide; indicating people with FAAH gene mutations may not have the appropriate levels of anandamide in the brain. Supplementing brains deficient in anandamide with THC may help restore chemical balances. Theoretically, this could alleviate cycling between manic and depressive phases.

Cannabidiol (CBD)

Cannabidiol has been shown to inhibit serotonin reuptake in rats, suggesting it repairs abnormalities in CB1 receptors found to inhibit release in mice. If CBD functions the same in human brains, it could provide an alternative to conventional antidepressants, especially for individuals with treatment-resistant BPAD.

A randomized clinical trial found CBD reduces abnormal brain function in regions associated with psychosis, implying it may have therapeutic effects on symptoms associated with the manic phase of BPAD. If CBD regulates both depressive and manic symptoms, it could help treat individuals who do not react well to lithium.

Other Cannabinoids

Cannabis is a complex compound, made up of over 500 chemicals. Over 100 of these compounds are suspected to be cannabinoids. There is little information on the effects of these chemicals, apart from CBD and THC, because few studies have focused on determining what reactions they produce in the EC system.

Among cannabinoids that have already been isolated, CBG and CBCV seem to show a potential for treating mood disorders, such as depression. Further study may help isolate more of these chemicals and determine what effect they have on the EC system.

A gloved scientist with a vial of CBD and a hemp leaf. Preliminary research supports further investigation into using CBD to treat bipolar affective disorder.

Though research is just beginning, it seems likely that CBD and other cannabinoids could help people with bipolar affective disorder.

USING CBDS & OTHER CANNABINOIDS FOR BIPOLAR AFFECTIVE DISORDER

CBD rarely causes adverse reactions. Still, there are risks associated with both conventional methods of treatment and using cannabis derivatives as treatment. The most dangerous side effect of any treatment for BPAD is the potential worsening of symptoms.

Individuals experiencing symptoms of bipolar affective disorder, or previously diagnosed with any of the variants, should consult with a medical professional before starting or changing treatment. Even those who present with treatment-resistant variations of the disease can benefit from traditional methods (such as psychotherapy).

Regulating the EC system through phytocannabinoids may provide a way to alleviate symptoms in those with treatment-resistant BPAD. Further clinical trials in humans are needed to validate preliminary data, but the future of cannabinoids as a BPAD treatment looks promising.

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Other Cannabinoids Revisited: More Natural Chemicals Found In Hemp

In this article, we continue our look at other cannabinoids found in hemp and cannabis. This time we examine four more cannabinoids — CBC-a, CBDV, CBG-a, and CBCV — and how they can benefit humanity.

In this article, we continue our look at other cannabinoids found in hemp and cannabis.

In July, we published our first look at different naturally occurring cannabinoids that are less well known than THC and CBD. There, we discussed the benefits of CBG (Cannabigerol), CBC (Cannabichromene), THCV (Tetrahydrocannabivarin), and CBN (Cannabinol). The article sparked some good discussion on social media and we’re hoping for the same with this one as we follow up with four more cannabinoids of note.

Preliminary research into the various other cannabinoids found in hemp and cannabis reveals that there's more to healing than just THC & CBD. Photo shows a hemp leaf surrounded by beakers of green fluid in a lab.

Preliminary research into the various other cannabinoids found in hemp and cannabis reveals that there’s more to healing than just THC & CBD.

This time, we’re going to discuss CBC-a (Cannabichromenic Acid), CBDV (Cannabidvarin), CBG-a (Cannabigerolic Acid), and CBCV (Cannabichromevarin). While these cannabinoids do show promise, they seem to be a lower priority for researchers. But hopefully, as researchers and scientists continue studying other cannabinoids, more information will become available on these lower tiered compounds.

CANNABICHROMENIC ACID (CBC-A)

The first cannabinoid we’re going to discuss is CBC-a (Cannabichromenic Acid).

CBC-a is the precursor to one of the most highly sought after cannabinoids, CBC (Cannabichromene). Like four other cannabinoids, CBC-A appears in the cannabis plant through decarbing. CBCA is non-psychoactive like CBD and has strong antimicrobial and analgesic (pain-relieving) properties. According to Maximum Yield, the most abundant levels of CBC-a are found in tropical strains of psychoactive cannabis (“marijuana”) with much lower levels found in other types of cannabis. According to current research, plants begin secreting cannabichromenic acid in the early seedling stage, before they create THC (Tetrahydrocannabinol). CBC-a can be converted to CBC through an aging and heating off the acid thru decarboxylation.

CBC-A Benefits:

  • Antimicrobial and analgesic properties
  • Anti-viral and anti-inflammatory

CANNABIDVARIN (CBDV)

Next up is CBDV (Cannabidvarin).

Like CBCA and most other cannabinoids we’ve discussed, CBDV is a non-psychoactive cannabinoid that has a similar makeup to CBD. Cannabis or hemp strains with higher levels of CBD tend to have higher levels of CBDV as well. Currently there hasn’t been much research on CBDV. Preliminary research shows that CBDV reduces nausea and seizures.

A researcher studies a hemp plant in a field. Hemp and cannabis contain numerous other cannabinoids beyond THC & CBD. These include CBC-a, CBDV, and many more.

Hemp and cannabis contain numerous other cannabinoids beyond THC & CBD. These include CBC-a, CBDV, and many more.

CBDV Benefits:

  • Anti-nausea. A study in 2013 by the British Journal of Pharmacology researched the potential of CBDV and THCV’s anti-nausea’s effect on rats’ brains. Researchers concluded that both cannabinoids “may have potential in reducing nausea.” Just by the quote alone, it’s apparent more research needs to be done.
  • Anti-seizures. Initial studies show that CBDV acts in a similar way to anti-convulsive medication Capsaicin, which targets the TRP channels (transient receptor potential channel) to combat the gradual process of brain development epilepsy. In fact, an Italian research team found that both CBDV and Capsaicin dephosphorylated TRPV1. CBDV’s effects on TRP channels are being studied to fully understand this cannabinoids anticonvulsive ability. One pharmaceutical company, GW Pharmaceuticals, is actively developing CBDV products for research in clinical trials. They are currently in a phase 2- trial CBDV product under the name GWP42006 that they’re hoping to be approved in treating adults with epilepsy.

CANNABIGEROLIC ACID (CBG-A)

The next in our list of other cannabinoids is CBG-a (Cannabigerolic Acid).

CBGA is considered the “cannabinoid stem cell.” Without CBGA, the amazing health benefits of THCa/THC, CBDa/CBD, CBCa/CBC, and CBG would not exist! These other cannabinoids form through biosynthesis, where chemicals combine to form new compounds. Studies show that industrial hemp contains high levels of CBGa, with some plants carrying up to 94% CBG!

CBG-A Benefits:

      • Analgesic. CBGa has been found to be an analgesic, meaning it provided pain relief.
      • Anti-bacterial. CBGA delays the growth of new bacteria.
      • Anti-inflammatory. CBGa reduces inflammation systematically.
      • Biosynthesis. Without CBGa the medicinal benefits of the other cannabinoids wouldn’t exist. This is important. So much so that scientists aren’t directly studying this cannabinoid. Instead, funding and research are all going to better understand how the biosynthesis itself works.

CANNABICHROMEVARIN (CBCV)

The last other cannabinoid we’re going to talk about is CBCV (Cannabichromevarin).

A researcher in a lab coat studies the leafy flower top of a hemp plant in a field. Research into other cannabinoids helps us understand how this amazing plant can benefit humanity.

Research into other cannabinoids helps us understand how this amazing plant can benefit humanity.

CBCV was first discovered in 1975 when researchers at the University of Nagasaki in Thailand islolated the compound from the cannabis plant. This cannabinoid is the precursor to Cannabichromene (CBC). Cannabis strains with lower levels of THC and CBD often have higher levels of CBCV.

CBCV Benefits:

  • Anti-convulsive.  One of the major benefits of CBCV is its anticonvulsant properties. Researchers from the Regents of the University of California have a patent on an anticonvulsant drug for infants dealing with seizures. Although the primary compound in the drug is CBD, the University of California mentions both CBCV and CBC in the patent as well.
  • Anandamide (AEA) reuptake inhibitor. Anandamide is a naturally occurring cannabinoid in humans. Researchers found that CBCV blocks Anandamide’s absorption by our brain and keeps it working for longer in our bodies.
  • Very similar medical benefits to CBC, CBCV is a powerful anti-inflammatory, antidepressant, antibiotic, analgesic and antifungal and may be beneficial for patients suffering from:
  1. Chronic pain
  2. Major depression
  3. Inflammation
  4. Cancer
  5. Epileptic seizures
  6. Crohn’s disease
  7. Alzheimer’s disease

WAR ON DRUGS INTERFERES WITH RESEARCH INTO OTHER CANNABINOIDS

In the span of two articles we shared 8 different cannabinoids, plus CBD and THC, which we discuss at great lengths in other articles. That’s 10 of the most researched and medically beneficial cannabinoids!

This time around we weren’t able to go as in-depth as we normally would in these types of articles because there just wasn’t enough information on these other cannabinoids just yet. We know scientists believe there are over 100 cannabinoids in the cannabis plant. Research and funding opportunities are still very limited. Cannabis and hemp are both classified as a Schedule I drug by the Drug Enforcement Administration. This classification means the agency refuses to acknowledge that these plants have any medical benefits, despite the evidence to the contrary.

Until this changes, the war on drugs limits our knowledge of the benefits of these miraculous plants. Fortunately, we believe that this will soon change for the better.

In the meantime, read and get to know the cannabinoids we shared, and learn about how they might help people like you.

 

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Fibromyalgia, Migraines & The Science Of Clinical Endocannabinoid Deficiency

First proposed by Dr. Ethan Russo, Clinical Endocannabinoid Deficiency could contribute to numerous painful conditions from fibromyalgia to IBS to migraine. This would help explain why cannabis and hemp help so many people with these conditions.

A theoretical syndrome, clinical endocannabinoid deficiency, could provide new insight into painful conditions suffered by millions.

Scientific advancements have helped us to find working treatments for countless debilitating conditions. However, there are some illnesses that continue to prove notorious and mysterious, with no known causes or cures. Research into the endocannabinoid system (ECS), a network in the body influenced by plant-derived cannabinoids, has provided medical experts with a fresh perspective on ailments such as fibromyalgia, irritable bowel syndrome (IBS) and migraines.

Dr Ethan Russo, a professional neurologist and cannabis researcher, first published the concept of a spectrum disorder in 2004. He first began working on the idea of dysregulation in the ECS in 2001. Both doctors and patients have noticed that cannabis and CBD oil seem to benefit people with these conditions. Russo has proposed that the effectiveness of cannabinoid medicine in the trio of aforementioned conditions can be explained by Clinical Endocannabinoid Deficiency (CECD).

A white paper cutout of a human head, missing a puzzle piece shaped hole, sits on a wooden surface. The puzzle piece, colored red, sits nearby. Though still theoretical, clinical endocannabinoid deficiency could be a common contributor to numerous conditions, from fibromyalgia to migraines.

Though still theoretical, clinical endocannabinoid deficiency could be a common contributor to numerous conditions, from fibromyalgia to migraines.

INTRODUCING CLINICAL ENDOCANNABINOID DEFICIENCY

For the ECS to function efficiently, the body must produce endocannabinoids (naturally occurring, cannabis-like chemicals) such as anandamide (AEA) and 2-Arachidonoylglycerol (2-AG).

However, studies have found that some people have lower endocannabinoid levels than others, which brings about health complications. There is an increasing body of clinical research which shows anxiety to be associated with reduced anandamide levels, and major depression to be linked with reduced 2-AG levels. When the body is unable to produce endocannabinoids in the concentrations required, chemical imbalances occur, which leads to illness.

Cannabinoid receptors interact with both endocannabinoids and cannabinoids, with the plant-derived compounds able to mimic endocannabinoids or otherwise influence them for ECS regulation. Therefore, it is logical that a cannabinoid treatment could effectively remedy CECD.

Russo’s latest significant update on his CECD research came in 2016, with a paper that continued to build on the concept, incorporating available clinical evidence. This followed an earlier 2008 release.

FIBROMYALGIA AND CLINICAL ENDOCANNABINOID DEFICIENCY

Medical researchers have been unable to come up with a definite cause for fibromyalgia. Patients suffer from an array of debilitating symptoms that have a significant effect on quality of life. These symptoms include chronic deep muscle and tender point pain, impaired cognitive function (or “fibro fog”), headaches, sleeping difficulties and restless leg syndrome. According to the Anxiety and Depression Association of America, 20 percent of fibromyalgia patients experience one of or both of these mental health disorders. Typically, this is a result of the pain and fatigue caused by the condition. In 2011, a study found that CBD could reduce anxiety beyond placebo levels, with patients given a 600mg dose administered via CBD capsules.

Moreover, several symptoms of fibromyalgia are indicative of ECS dysregulation — for instance, inflammatory conditions occur due to problems with immune system response, which is modulated by the ECS and specifically the CB2 receptor. Studies have also found that serotonin levels are affected in fibromyalgia patients, which may be noteworthy considering CBD is an agonist of the 5-HT1A receptor.

MIGRAINES AND CLINICAL ENDOCANNABINOID DEFICIENCY

Around 39 million Americans are affected by migraines, according to the Migraine Research Foundation. Migraines can cause dizziness, nausea, numbness or tingling in the face and other unpleasant symptoms. Research has shown that migraine sufferers have “statistically significant” differences in anandamide levels in cerebrospinal fluid, which is found in the brain and spinal cord.

A woman clutches her head in pain, as if suffering from a migraine. Migraine sufferers have been shown to have lower levels of anandamide, a naturally occurring chemical found in all people that's similar to those found in cannabis and hemp.

Migraine sufferers have been shown to have lower levels of anandamide, a naturally occurring chemical found in all people that’s similar to those found in cannabis and hemp.

Russo found that endocannabinoid system changes could help to alleviate migraines in his 2004 research. The main finding was that anandamide, a key neurotransmitter in the ECS, heightens the effectiveness of the 5-HT1A receptor while inhibiting the 5-HT2A receptor. This could help with treating acute migraines and as a preventative treatment. Furthermore, the results showed that several cannabinoids exhibited anti-inflammatory properties and dopamine-blocking effects.

The light and sound sensitivity that results from migraines may be due to an overactive nervous system. The ECS is renowned for regulating such imbalances (Russo, 2016). Some have suggested that the root cause of migraines can be traced back to the trigeminovascular system, which brings blood to the brain. Studies have shown that endocannabinoids can influence this system. Migraines and cluster headaches may be best managed with a treatment that is an agonist of the CB1 receptor.

In the case of migraines, one study found that while a CBD and THC treatment was not necessarily more effective than existing anti-migraine treatments, the side effects were significantly reduced.

Fascinatingly, cannabis was a common treatment for migraines in Europe and North America from the mid-1800s until the 1940s, a time when the herb was being prohibited around the globe.

NEXT STEPS IN CANNABINOID RESEARCH

As governments all over the world look into the benefits of medical cannabis, the number of high-quality studies being carried out in clinical settings is sure to increase.

With time, we should get an in-depth look at the potential of cannabinoids as a treatment for fibromyalgia, migraines and other illnesses. As our understanding of the ECS deepens, we may learn more about the wide-scale implications of dysfunction in the system.

A gloved scientist with a vial of CBD and a hemp leaf. 'Full spectrum' extracts contain more cannabinoids, terpenes, and other beneficial chemicals found in hemp & cannabis.

A gloved scientist with a vial of CBD and a hemp leaf. ‘Full spectrum’ extracts contain more cannabinoids, terpenes, and other beneficial chemicals found in hemp & cannabis.

Furthermore, more research needs to be done on the possible interactions cannabinoids have with receptors outside of the ECS and the effects this may have on the body.

CLINICAL ENDOCANNABINOID DEFICIENCY SHOWS HOW MUCH WE HAVE LEFT TO LEARN

It’s essential to bear in mind that the work of Dr Russo and others on CECD is at the forefront of cannabis science, and we still have plenty to learn about the endocannabinoid system, the effects of its dysregulation, and the genuine potential of cannabinoid-based medicines for treating notoriously complicated conditions such as fibromyalgia.

However, the theory has certainly fleshed out since 2004. There are studies that suggest medical cannabis and CBD can have a therapeutic effect for certain conditions. But in his 2016 paper, Russo noted that contradictions in CECD research were common. He reported that excessive levels of endocannabinoids could also be damaging for health, potentially leading to obesity and hepatic fibrosis.

Regulation of the endocannabinoid system is probably not be as simple as taking a dose of CBD or THC. There are dozens of cannabinoids in hemp and cannabis. Research indicates that whole-plant tinctures can be preferable to isolates of just one chemical. Given that endocannabinoid imbalances differ from patient to patient, the ideal medication for these imbalances may vary too. Perhaps someday, these treatments may be more be tailored to fit a person’s exact illness.

It’s clear we still have a lot more to learn about the endocannabinoid system before we can fully understand how it contributes to our health and well-being.

 

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