Anti-depressant effects of ethanol extract from Cannabis sativa (hemp) seed in chlorpromazine-induced Drosophila melanogaster depression model

Posted on August 8, 2021 by David Worrell

“Context: Depression is a severe mental illness caused by a deficiency of dopamine and serotonin. Cannabis sativa L. (Cannabaceae) has long been used to treat pain, nausea, and depression.

Objective: This study investigates the anti-depressant effects of C. sativa (hemp) seed ethanol extract (HE) in chlorpromazine (CPZ)-induced Drosophila melanogaster depression model.

Results: The behavioural patterns of individual flies were significantly reduced with 0.1% CPZ treatment. In contrast, combination treatment of 1.5% HE and 0.1% CPZ significantly increased subjective daytime activity (p < 0.001) and behavioural factors (p < 0.001). These results correlate with increased transcript levels of dopamine (p < 0.001) and serotonin (p < 0.05) receptors and concentration of dopamine (p < 0.05), levodopa (p < 0.001), 5-HTP (p < 0.05), and serotonin (p < 0.001) compared to those in the control group.

Discussion and conclusions: Collectively, HE administration alleviates depression-like symptoms by modulating the circadian rhythm-related behaviours, transcript levels of neurotransmitter receptors, and neurotransmitter levels in the CPZ-induced Drosophila model. However, additional research is needed to investigate the role of HE administration in behavioural patterns, reduction of the neurotransmitter, and signalling pathways of depression in a vertebrate model system.”

https://pubmed.ncbi.nlm.nih.gov/34362287/

“CPZ induces depression-like symptoms, such as changes in behavioural patterns, transcription levels of neurotransmitter receptors, and depression-related neurotransmitter levels in the D. melanogaster depression model. However, administration of HE restores the circadian rhythms, improves locomotor activity, and significantly increases transcription levels of dopamine and serotonin receptors in the depression-induced flies. Based on these findings, we can conclude that HE alleviates depression-like symptoms by increasing the levels of serotonin and dopamine receptors and dopamine, L-DOPA, 5-HTP, and serotonin levels in the brain.”

https://www.tandfonline.com/doi/full/10.1080/13880209.2021.1949356

The Pro-neurogenic Effects of Cannabidiol and Its Potential Therapeutic Implications in Psychiatric Disorders

Posted on July 17, 2020 by David Worrell

“During the last decades, researchers have investigated the functional relevance of adult hippocampal neurogenesis in normal brain function as well as in the pathogenesis of diverse psychiatric conditions.

Although the underlying mechanisms of newborn neuron differentiation and circuit integration have yet to be fully elucidated, considerable evidence suggests that the endocannabinoid system plays a pivotal role throughout the processes of adult neurogenesis. Thus, synthetic, and natural cannabinoid compounds targeting the endocannabinoid system have been utilized to modulate the proliferation and survival of neural progenitor cells and immature neurons.

Cannabidiol (CBD), a constituent of the Cannabis Sativa plant, interacts with the endocannabinoid system by inhibiting fatty acid amide hydrolase (FAAH) activity (the rate-limiting enzyme for anandamide hydrolysis), allosterically modulating CB1 and CB2 receptors, and activating components of the “extended endocannabinoid system.” Congruently, CBD has shown prominent pro-neurogenic effects, and, unlike Δ⁹-tetrahydrocannabinol, it has the advantage of being devoid of psychotomimetic effects.

Here, we first review pre-clinical studies supporting the facilitating effects of CBD on adult hippocampal neurogenesis and available data disclosing cannabinoid mechanisms by which CBD can induce neural proliferation and differentiation. We then review the respective implications for its neuroprotective, anxiolytic, anti-depressant, and anti-reward actions.

In conclusion, accumulating evidence reveals that, in rodents, adult neurogenesis is key to understand the behavioral manifestation of symptomatology related to different mental disorders. Hence, understanding how CBD promotes adult neurogenesis in rodents could shed light upon translational therapeutic strategies aimed to ameliorate psychiatric symptomatology dependent on hippocampal function in humans.”

https://pubmed.ncbi.nlm.nih.gov/32676014/

https://www.frontiersin.org/articles/10.3389/fnbeh.2020.00109/full

Effects of cannabidiol (CBD) in neuropsychiatric disorders: A review of pre-clinical and clinical findings.

Posted on October 12, 2019 by David Worrell

Progress in Molecular Biology and Translational Science “Cannabis sativa (cannabis) is one of the oldest plants cultivated by men. Cannabidiol (CBD) is the major non-psychomimetic compound derived from cannabis. It has been proposed to have a therapeutic potential over a wide range of neuropsychiatric disorders.

In this narrative review, we have summarized a selected number of pre-clinical and clinical studies, examining the effects of CBD in neuropsychiatric disorders. In some pre-clinical studies, CBD was demonstrated to potentially exhibit anti-epileptic, anti-oxidant, anti-inflammatory anti-psychotic, anxiolytic and anti-depressant properties. Moreover, CBD was shown to reduce addictive effects of some drugs of abuse.

In clinical studies, CBD was shown to be safe, well-tolerated and efficacious in mitigating the symptoms associated with several types of seizure disorders and childhood epilepsies.

Given that treatment with CBD alone was insufficient at managing choreic movements in patients with Huntington’s disease, other cannabis-derived treatments are currently being investigated. Patients with Parkinson’s disease (PD) have reported improvements in sleep and better quality of life with CBD; however, to fully elucidate the therapeutic potential of CBD on the symptoms of PD-associated movement disorders, larger scale, randomized, placebo-controlled studies still need to be conducted in the future.

Currently, there are no human studies that investigated the effects of CBD in either Alzheimer’s disease or unipolar depression, warranting further investigation in this area, considering that CBD was shown to have effects in pre-clinical studies.

Although, anxiolytic properties of CBD were reported in the Social Anxiety Disorder, antipsychotic effects in schizophrenia and anti-addictive qualities in alcohol and drug addictions, here too, larger, randomized, placebo-controlled trials are needed to evaluate the therapeutic potential of CBD.”

https://www.ncbi.nlm.nih.gov/pubmed/31601406

https://www.sciencedirect.com/science/article/pii/S187711731930095X?via%3Dihub

The “entourage effect”: Terpenes coupled with cannabinoids for the treatment of mood disorders and anxiety disorders.

Posted on September 5, 2019 by David Worrell

“Mood disorders are the most prevalent mental conditions encountered in psychiatric practice. Numerous patients suffering from mood disorders present with treatment-resistant forms of depression, co-morbid anxiety, other psychiatric disorders and bipolar disorders.

Standardized essential oils (such as that of Lavender officinalis) have been shown to exert clinical efficacy in treating anxiety disorders. As endocannabinoids are suggested to play an important role in major depression, generalized anxiety and bipolar disorders, Cannabis sativa, was suggested for their treatment.

The endocannabinoid system is widely distributed throughout the body including the brain, modulating many functions. It is involved in mood and related disorders, and its activity may be modiﬁed by exogenous cannabinoids.

CB1 and CB2 receptors primarily serve as the binding sites for endocannabinoids as well as for phytocannabinoids, produced by cannabis inflorescences. However, ‘cannabis’ is not a single compound product but is known for its complicated molecular profile, producing a plethora of phytocannabinoids alongside a vast array of terpenes.

Thus, the “entourage effect” is the suggested positive contribution derived from the addition of terpenes to cannabinoids. Here we review the literature on the effects of cannabinoids and discuss the possibility of enhancing cannabinoid activity on psychiatric symptoms by the addition of terpenes and terpenoids.

Possible underlying mechanisms for the anti-depressant and anxiolytic effects are reviewed. These natural products may be an important potential source for new medications for the treatment of mood and anxiety disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/31481004

http://www.eurekaselect.com/174648/article

Repetitive high-frequency transcranial magnetic stimulation reverses depressive-like behaviors and protein expression at hippocampal synapses in chronic unpredictable stress-treated rats by enhancing endocannabinoid signaling.

Posted on June 25, 2019 by David Worrell

Pharmacology Biochemistry and Behavior “The anti-depressant effect of repetitive transcranial magnetic stimulation (rTMS), a clinically-useful treatment for depression, is associated with changes to the endocannabinoid system (ECS).

However, it is currently unknown whether different frequencies of rTMS alter the ECS differently. To test this, rats exposed to chronic unpredictable stress (CUS) were treated with rTMS at two different frequencies (5 (high) or 1 Hz (low), 1.26 Tesla) for 7 consecutive days.

Interestingly, we found that only high-frequency rTMS ameliorated depressive-like behaviors and normalized the expression of hippocampal synaptic proteins in CUS-treated rats;

Collectively, our results suggest that high-frequency rTMS exerts its anti-depressant effect by up-regulating diacylglycerol lipase alpha (DAGLα) and cannabinoid type 1 receptor (CB1R).”

https://www.ncbi.nlm.nih.gov/pubmed/31229467

https://www.sciencedirect.com/science/article/pii/S0091305719301376?via%3Dihub

“Transcranial magnetic stimulation (TMS), also known as repetitive transcranial magnetic stimulation (rTMS), is a noninvasive form of brain stimulation in which a changing magnetic field is used to cause electric current at a specific area of the brain through electromagnetic induction. An electric pulse generator, or stimulator, is connected to a magnetic coil, which in turn is connected to the scalp. The stimulator generates a changing electric current within the coil which induces a magnetic field; this field then causes a second inductance of inverted electric charge within the brain itself. Adverse effects of TMS are rare, and include fainting and seizure. Other potential issues include discomfort, pain, hypomania, cognitive change, hearing loss, and inadvertent current induction in implanted devices such as pacemakers or defibrillators” https://www.sciencedirect.com/science/article/pii/S0091305719301376?via%3Dihub

Is Cannabidiol a Promising Substance for New Drug Development? A Review of its Potential Therapeutic Applications.

Posted on May 19, 2018 by David Worrell

Critical Reviewsâ¢ in Eukaryotic Gene Expression

“The pharmacological importance of cannabidiol (CBD) has been in study for several years. CBD is the major nonpsychoactive constituent of plant Cannabis sativa and its administration is associated with reduced side effects. Currently, CBD is undergoing a lot of research which suggests that it has no addictive effects, good safety profile and has exhibited powerful therapeutic potential in several vital areas. It has wide spectrum of action because it acts through endocannabinoid receptors; CB1 and CB2 and it also acts on other receptors, such as GPR18, GPR55, GPR 119, 5HT1A, and TRPV2. This indicates its therapeutic value for numerous medical conditions because of its neuroprotective and immunomodulatory properties. Potential therapeutic applications of CBD include, analgesic, anti-inflammatory, anxiolytic, anti-arthritic, anti-depressant, anti-Alzheimer disease, anti-ischemic, neuroprotective, and anti-fibrotic. More promising areas appear to include diabetes and cancer where CBD exhibits lesser side effects and more therapeutic benefits as compared to recent available medical therapies. Hence, CBD is a promising substance for the development of new drug. However further research and clinical studies are required to explore its complete potential.”

https://www.ncbi.nlm.nih.gov/pubmed/29773016

http://www.dl.begellhouse.com/journals/6dbf508d3b17c437,642ad759707fc517,35856ff546e47ff9.html

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Decreased depression in marijuana users.

Posted on August 13, 2016 by David Worrell

“Over 4400 adult internet users completed The Center for Epidemiologic Studies Depression scale and measures of marijuana use.

We employed an internet survey in an effort to recruit the most depressed and marijuana-involved participants, including those who might prove unwilling to travel to the laboratory or discuss drug use on the phone or in person.

We compared those who consumed marijuana daily, once a week or less, or never in their lives.

Despite comparable ranges of scores on all depression subscales, those who used once per week or less had less depressed mood, more positive affect, and fewer somatic complaints than non-users.

Daily users reported less depressed mood and more positive affect than non-users.

These data suggest that adults apparently do not increase their risk for depression by using marijuana.”

http://www.ncbi.nlm.nih.gov/pubmed/15964704

New Study Finds Marijuana To Be Effective Against Depression, Migraine and Anxiety

Posted on July 28, 2016 by David Worrell

“Research has suggested that cannabis may be a promising treatment option for a number of different physical and mental health conditions, from post-traumatic stress disorder to chronic pain. A study released this week suggests that depression , anxiety and migraine can be added to that list.

Neuroscientists from the University of Buffalo’s Research Institute on Addictions found that endocannabinoids — chemical compounds in the brain that activate the same receptors as THC, an active compound in marijuana — may be helpful in treating depression, anxiety and migraine that results from chronic stress.

In studies on rats, the researchers found that chronic stress reduced the production of endocannabinoids, which affect our cognition, emotion and behavior, and have been linked to reduced feelings of pain and anxiety, increases in appetite and overall feelings of well-being. The body naturally produces these compounds, which are similar to the chemicals in cannabis. Reduction of endocannabinoid production may be one reason that chronic stress is a major risk factor in the development of depression.

Then, the research team administered marijuana cannabinoids to the rats, finding it to be an effective way to restore endocannabinoid levels in their brains — possibly, thereby, alleviating some symptoms of depression.

“Using compounds derived from cannabis — marijuana — to restore normal endocannabinoid function could potentially help stabilize moods and ease depression,” lead researcher Dr. Samir Haj-Dahmane said in a university press release.

Recent research around marijuana’s effect on symptoms of post-traumatic stress disorder further bolsters the Buffalo neuroscientists’ findings, since both disorders involve the way the brain responds to stress. A study published last year in the journal Neuropsychopharmacology, for instance, found synthetic cannabinoids triggered changes in brain centers associated with traumatic memories in rats, preventing some of the behavioral and physiological symptoms of PTSD. Another study published last year found that patients who smoked cannabis experienced a 75 percent reduction in PTSD symptoms.

However, it’s important to note that the relationship between marijuana and depression is complex. Some research has suggested that regular and heavy marijuana smokers are at a higher risk for depression, although a causal link between cannabis use and depression has not been established. More studies are needed in order to determine whether, and how, marijuana might be used in a clinical context for patients with depression.” http://painphysicianjournal.co/2016/06/30/new-study-finds-marijuana-to-be-effective-against-depression-migraine-and-anxiety/

http://painphysicianjournal.co/2016/06/30/new-study-finds-marijuana-to-be-effective-against-depression-migraine-and-anxiety/

Medical Marijuana Is Safe for Children

Posted on January 21, 2013 by David Worrell

“Numerous cases show clinical cannabis is effective on illnesses in children”

By William Courtney, M.D. William Courtney, M.D. is CEO of Cannabis International.

“The courage and fortitude of parents who have chosen cannabis compounds to treat their children facing life-threatening illness have raised eyebrows. Some live in terror that their government will take their child away, since medical marijuana is only legal in some states. However, there are numerous cases demonstrating the benefits of clinical cannabis, which happen to threaten a very profitable healthcare industry that relies on conventional drugs, as well as political agendas.

The cannabinoid acids in cannabis have been found to have anti-proliferative, anti-neoplastic, anti-inflammatory, anti-epileptic, anti-ischemic, anti-diabetic, anti-psychotic, anti-nausea, anti-spasmodic, antibiotic, anti-anxiety, and anti-depressant functions. The anti-neoplastic action of cannabis—inhibiting development of malignant cells—was recognized in the 1970s and patented by the U.S. Department of Health and Human Services in 2003.

Out of 7,000 patients, my youngest, an 8-month-old, was diagnosed with a massive midbrain tumor. Pediatric oncologists recommended chemotherapy and radiation. Instead, the parents applied a cannabinoid concentrate to their son’s pacifier twice a day, which resulted in a significant reduction in the size of the tumor in 30 days. The response prevented a million-dollar chemo-radiation hospitalization. The child’s oncologist calls the infant a ‘miracle baby,’ but most medical experts would discount the case as anecdotal, unacceptable in a peer-reviewed journal. But the real peers are other parents reluctant to consent to the devastation of surgery, chemotherapy, and radiation—not those benefiting from the $2.6 trillion healthcare industry.

A 2-year-old spent a year in a pediatric oncology ward, endured 39 hours of brain surgery, received chemotherapy, a bone marrow transplant, and radiation under general anesthesia for 42 days, only to be discharged home on hospice and morphine. The child’s local pediatrician started to treat her with juiced raw cannabis leaf. Two years later, she is still alive, now free of cancer and scar tissue.

A 6-year-old patient with a severe, intractable form of childhood epilepsy, was tried on 11 anti-epileptics, including experimental European drugs. He was finally placed on a drug commonly used to prevent seizures, but continued having 300-400 seizures a day. An ointment produced from cannabis with an increased amount of cannabidiol, a compound patented by HHS, has reduced his seizures to one every 3-4 days.

Several years ago, I proposed that cannabis be recognized as an essential nutrient in the diet of individuals in their 30s and older. Children were excluded out of fear of backlash but it is now my incontrovertible opinion that the immune system of the 8-month-old would never have allowed the tumor to gain a foothold if supported with dietary cannabis, or Vitamin F.

We know Vitamin C deficiency results in scurvy and Vitamin D deficiency results in rickets. Vitamin F, the previous label for Omega-3 and -6 essential fatty acids, is an appropriate appellation for the cannabinoid acids found in cannabis. Vitamin F deficiency allows the cell proliferation found in tumors and cancer. Three studies of over 24,000 children have shown no adverse effects from use of cannabis in pregnancy.

There is no other area in medicine where the heavy hand of federal funding and political agenda compromise valid and reproducible findings to this extent. To advance disease prevention and benign therapy, we must re-examine our preconceptions.”

http://www.usnews.com/opinion/articles/2013/01/07/medical-marijuana-is-safe-for-children

The endogenous cannabinoid anandamide has effects on motivation and anxiety that are revealed by fatty acid amide hydrolase (FAAH) inhibition

Posted on January 18, 2013 by David Worrell

“Converging evidence suggests that the endocannabinoid system is an important constituent of neuronal substrates involved in brain reward processes and emotional responses to stress.. It is known that the endocannabinoid system plays a modulatory role in emotional states such as anxiety and fear. Several studies utilizing rodent models of anxiety or depression showed that FAAH inhibition produced anxiolytic-like effects and anti-depressant-like effects…

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213536/

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