ACEA (a highly selective cannabinoid CB1 receptor agonist) stimulates hippocampal neurogenesis in mice treated with antiepileptic drugs.

“Hippocampal neurogenesis plays a very important role in learning and memory functions.

In a search for best neurological drugs that protect neuronal cells and stimulate neurogenesis with no side effects, cannabinoids proved to be a strong group of substances having many beneficial properties.

The aim of this study was to evaluate the impact of ACEA (arachidonyl-2′-chloroethylamide – a highly selective cannabinoid CB1 receptor agonist) combined with a classical antiepileptic drug sodium valproate (VPA) on neural precursor cells’ proliferation and differentiation in the mouse brain.

VPA administered alone decreased the number of newly born neurons with no significant impact on neurogenesis.

These data provide substantial evidence that VPA administered chronically slightly decreases the proliferation and differentiation of newly born cells while combination of VPA+ACEA significantly increases the level of newborn neurons in the dentate subgranular zone.”

http://www.ncbi.nlm.nih.gov/pubmed/26225920

The role of cannabinoids in adult neurogenesis.

“Cannabinoids are a unique class of chemical compounds incorporating plant-derived cannabinoids (the active components of Cannabis sativa), the endogenous cannabinoids and synthetic cannabinoid ligands, and these compounds are becoming increasingly recognized for their roles in neural developmental processes.

Indeed, cannabinoids have clear modulatory roles in adult neurogenesis, likely through activation of both CB1 and CB2receptors.

In recent years a large body of literature has deciphered the signalling networks involved in cannabinoid-mediated regulation of neurogenesis. This timely review summarises the evidence that the cannabinoid system is intricately associated with neuronal differentiation and maturation of NPCs, and highlights intrinsic/extrinsic signalling mechanisms that are cannabinoid targets.

Overall these findings identify the central role of the cannabinoid system in adult neurogenesis in the hippocampus and the lateral ventricles, and hence provide insight into the processes underlying post-developmental neurogenesis in the mammalian brain.”

Pharmacological blockade of the fatty acid amide hydrolase (FAAH) alters neural proliferation, apoptosis and gliosis in the rat hippocampus, hypothalamus and striatum in a negative energy context.

“Endocannabinoids participate in the control of neurogenesis, neural cell death and gliosis.

The pharmacological effect of the fatty acid amide hydrolase (FAAH) inhibitor URB597, which limits the endocannabinoid degradation, was investigated in the present study…

Main results indicated that FAAH inhibitor URB597 decreased neural proliferation, glia and apoptosis in a brain region-dependent manner, which were coupled to local changes in Faah and/or Cnr1 expression and a negative energy context.”

http://www.ncbi.nlm.nih.gov/pubmed/25870539

Mechanisms of control of neuron survival by the endocannabinoid system.

“Endocannabinoids act as retrograde messengers that, by inhibiting neurotransmitter release via presynaptic CB(1) cannabinoid receptors, regulate the functionality of many synapses. In addition, the endocannabinoid system participates in the control of neuron survival.

Thus, CB(1) receptor activation has been shown to protect neurons from acute brain injury as well as in neuroinflammatory conditions and neurodegenerative diseases.

Cannabinoid neuroprotective activity relies on the inhibition of glutamatergic neurotransmission and on other various mechanisms, and is supported by the observation that the brain overproduces endocannabinoids upon damage.

Besides promoting neuroprotection, a role for the endocannabinoid system in the control of neurogenesis from neural progenitors has been put forward. In addition, activation of CB(2) cannabinoid receptors on glial cells may also participate in neuroprotection by limiting the extent of neuroinflammation.

Altogether, these findings support that endocannabinoids constitute a new family of lipid mediators that act as instructive signals in the control of neuron survival.”

http://www.ncbi.nlm.nih.gov/pubmed/18781978

Defective Adult Neurogenesis in CB1 Cannabinoid Receptor Knockout Mice

  Fig. 1.

“…endogenous cannabinoid signaling mechanisms may represent a key component of cell-survival programs mobilized in the injured brain.

In addition to their neuroprotective effects, cannabinergic systems may also have an important role in brain development…

…expression of endocannabinoids and cannabinoid receptors in brain…

Neurogenesis, or the birth of new neurons, continues to occur beyond development and into adulthood, and several lines of evidence suggest that cannabinoid signaling may be involved in this process as well…

In addition to the well known effects of growth factors, a variety of drugs has been shown to influence adult neurogenesis. These include excitatory amino acid receptor antagonists, antidepressants, lithium, nitric oxide donors, phosphodiesterase inhibitors, and statins.

Together with the finding that neurogenesis can be regulated by cannabinoids, these observations imply that a broad range of pharmacological approaches may exist through which to modify neurogenesis for therapeutic purposes.”

http://molpharm.aspetjournals.org/content/66/2/204.full

Marijuana May Grow Neurons in the Brain

Medpage Today

“Advocates for medical marijuana can take heart over the findings of two Canadian research teams.

A synthetic cannabinoid — similar to the compounds found in marijuana, but substantially stronger — causes the growth of new neurons and reduces anxiety and depression, investigators at the University of Saskatchewan here reported.

And researchers at the University of Calgary said they’ve found evidence that the brain contains so-called CB2 cannabinoid receptors, previously seen in immune tissue but thought not to exist in brain tissue. The discovery, they added, could lead to new drugs to treat nausea associated with cancer or AIDS.

Most so-called drugs of abuse — such as alcohol or cocaine — inhibit the growth of new neurons, according to Xia Zhang, M.D., Ph.D., of the University of Saskatchewan.

“Only marijuana promotes neurogenesis,” Dr. Zhang said.”

http://www.medpagetoday.com/Psychiatry/AnxietyStress/1934

“Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects… In summary, since adult hippocampal neurogenesis is suppressed following chronic administration of opiates, alcohol, nicotine, and cocaine, the present study suggests that cannabinoids are the only illicit drug that can promote adult hippocampal neurogenesis following chronic administration.”  http://www.jci.org/articles/view/25509

University Of Saskatchewan Research Suggests Marijuana Analogue Stimulates Brain Cell Growth

ScienceDaily: Your source for the latest research news

“A synthetic substance similar to ones found in marijuana stimulates cell growth in regions of the brain associated with anxiety and depression, pointing the way for new treatments for these diseases, according to University of Saskatchewan medical research published today in The Journal of Clinical Investigation.

Xia Zhang, an associate professor in the U of S neuropsychiatry research unit, led the team that tested the effects of HU-210, a potent synthetic cannabinoid similar to a group of compounds found in marijuana. The synthetic version is about 100 times as powerful as THC, the compound responsible for the high experienced by recreational users.

The team found that rats treated with HU-210 on a regular basis showed neurogenesis – the growth of new brain cells in the hippocampus. This region of the brain is associated with learning and memory, as well as anxiety and depression.

The effect is the opposite of most legal and illicit drugs such as alcohol, nicotine, heroin, and cocaine.

“Most ‘drugs of abuse’ suppress neurogenesis,” Zhang says. “Only marijuana promotes neurogenesis.””

http://www.sciencedaily.com/releases/2005/10/051016083817.htm

“Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects… In summary, since adult hippocampal neurogenesis is suppressed following chronic administration of opiates, alcohol, nicotine, and cocaine, the present study suggests that cannabinoids are the only illicit drug that can promote adult hippocampal neurogenesis following chronic administration.”  http://www.jci.org/articles/view/25509

Chronic cannabidiol treatment improves social and object recognition in double transgenic APPswe/PS1∆E9 mice.

“Patients suffering from Alzheimer’s disease (AD) exhibit a decline in cognitive abilities including an inability to recognise familiar faces…

The non-psychoactive phytocannabinoid cannabidiol (CBD) exerts neuroprotective, anti-oxidant and anti-inflammatory effects and promotes neurogenesis. CBD also reverses Aβ-induced spatial memory deficits in rodents.

This is the first study to investigate the effect of chronic CBD treatment on cognition in an AD transgenic mouse model.

Our findings suggest that CBD may have therapeutic potential for specific cognitive impairments associated with AD.”

http://www.ncbi.nlm.nih.gov/pubmed/24577515

Pharmacological blockade of either cannabinoid CB1 or CB2 receptors prevents both cocaine-induced conditioned locomotion and cocaine-induced reduction of cell proliferation in the hippocampus of adult male rat.

“Addiction to major drugs of abuse, such as cocaine, has recently been linked to alterations in adult neurogenesis in the hippocampus. The endogenous cannabinoid system modulates this proliferative response as demonstrated by the finding that pharmacological activation/blockade of cannabinoid CB1 and CB2 receptors not only modulates neurogenesis but also modulates cell death in the brain.

In the present study, we evaluated whether the endogenous cannabinoid system affects cocaine-induced alterations in cell proliferation…

These results indicate that the changes in neurogenic, apoptotic and gliotic processes that were produced by repeated cocaine administration were normalized by pharmacological blockade of CB1 and CB2. The restorative effects of cannabinoid receptor blockade on hippocampal cell proliferation were associated with the prevention of the induction of conditioned locomotion but not with the prevention of cocaine-induced sensitization.”

http://www.ncbi.nlm.nih.gov/pubmed/24409127

Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects.

115-11-cover

“Cannabis (marijuana, hashish, or cannabinoids) has been used for medical and recreational purposes for many centuries and is likely the only medicine or illicit drug that has constantly evoked tremendous interest or controversy within both the public domain and medical research. Cannabinoids appear to be able to modulate pain, nausea, vomiting, epilepsy, ischemic stroke, cerebral trauma, multiple sclerosis, tumors, and other disorders in humans and/or animals.

Cannabis acts on 2 types of cannabinoid receptors, the CB1 and CB2 receptors, which are distributed mainly in the brain and immune system, respectively. In the brain, CB1 receptors are also targeted by endogenous cannabinoids (i.e., endocannabinoids) such as anandamide (AEA), 2-arachidonylglycerol, and arachidonylethanolamide…

…since adult hippocampal neurogenesis is suppressed following chronic administration of opiates, alcohol, nicotine, and cocaine, the present study suggests that cannabinoids are the only illicit drug that can promote adult hippocampal neurogenesis following chronic administration…

Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects.”  

https://www.jci.org/articles/view/25509

“University Of Saskatchewan Research Suggests Marijuana Analogue Stimulates Brain Cell Growth”  http://www.sciencedaily.com/releases/2005/10/051016083817.htm