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

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“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

Alzheimer’s, Mom and Cannabis

“It is Skunk PharmResearch’s policy to let patients tell their own story, but in the case of mom, as her daughter and 24/7 caregiver, I will speak for her.  She is in the late seventh and final stage of Alzheimer’s and would want her story told.

Mom was diagnosed as late stage six when she came to me from Seattle four years ago.  She was given six more months to live. She began displaying symptoms before 1998, but she wasn’t diagnosed until 2001, following her first husband’s death.  It took that long to resolve other health issues and get her to a neurologist.

Just the thought of Alzheimer’s frightened her so, that we eventually had to trick her, to get her to a doctor for testing.   Once tested and diagnosed, they put her on Aricept, which brought back cognitive skills, with slow decline for the next seven years while my step brother cared for her in her own home.  Along with other western meds, this was her medical course.

When Mom’s Alzheimer’s progressed to the point that she became combative and personal hygiene became an issue, my brother planned to put her in a nursing home, but I quit my job to look after her.  I moved her to Portland with me and took over her care, to focus on the quality of her remaining life.

For five months prior to her arrival, I immersed myself into learning as much about Alzheimer’s as possible, researching and joining The Alzheimer’s Association, as well as the Online Alzheimer’s Support Group, spending as much time as possible conversing with patients and caregivers alike, to prepare myself for the task.

When Mom arrived, besides being on five over the counter drugs, she was on three inhalers and a pill for asthma, blood pressure meds, allergy meds, anti psychotics that made her angry, anti seizure meds that made her delusional, plus three others I have no idea what they were used to combat.

We got her an OMMP card immediately upon her arrival.  She had smoked cannabis recreationally with me for over thirty years, but never medically until she came toOregon. Cannabis was my only means of mitigating her despicable behavior (psychotic).

Her physical health was also poor, so I changed her diet, eliminated dairy, wheat and gluten. I prepared and feed her home cooked meals, using whole organic ingredients, supplemented with quality vitamins and minerals.

I’ve continued to work with her doctor to straighten out her mishmash of meds.  He started with large doses of anti psychotics to combat the behavioral issues (with potential seizure/death side effect), and we systematically took her off as many of the other drugs as possible.  Meanwhile, I started trying the different forms of cannabis concentrates.

The first extractions were cannabis essential oils using hot grape seed oil, but she didn’t like the flavor and refused to ingest it.

Given that unused meds are 100% ineffective, I next tried honey elixir, thinking she might go for the sweetness of the honey, but no luck.

No luck with fudge either, even though she loves chocolate.

I quickly determined that the only way to get substantial doses into mom would be via concentrates, so after experimenting with bubble hash combined with coconut oil as a menstruum, I focused on hash oil in an effort to improve consistency and homogeneity for consistency in dosing.

More specifically I began to experiment on my version of the Holy Anointing Oil from Exodus, using coconut oil instead of olive oil, and brewed from essential oils, as opposed to using the biblical perfumer’s extraction practices.

More on that medication at:  http://skunkpharmresearch.com/holy-anointing-oil-and-holy-shit/

It worked beautifully!  The flavor of the cannabis was concealed by the remaining essential oils in the ingredients.  She loved it, and to my delight, she became happier and less combative.

Mom transformed from aggressive and angry to the cheerful woman I knew from childhood.  Instead of slapping my cheeks, she caressed them tenderly and moved my hair from my face as she told me she loved me.  From her isolation came the interaction and humor required to joke with us.   From frantic shuffling and hiding of objects she began offering them for my use.  Rather then kicking, biting and hitting, she became happily compliant, even cooperative.  She literally became a social butterfly!

Mom also suffered extensively from muscle spasms, particularly in her legs, typically relieved by dancing the night away together. But one night I thinned some HAO oral with coconut oil, to reduce the cinnamon oil below topical TLV as an irritant and to improve penetration.  After slathering her leg with the modified HAO, the cramps went away, allowing her to go back to sleep.  She woke 20 minutes later complaining of the other leg.  Again, HAO topical and back to sleep! HAOT was born.

It took nearly two years working with her doctor to get her medical care stabilized and a permanent “Primary Care Practitioner” (PCP) established.  We were able to get her off of most of the original drug regiment, and determined that her psychotic episodes were directly related to urinary tract infections, for which she is susceptible.

With cultures and medications, we were able to get the UTIs in check which eliminated the need for the anti psychotic, Seroquil.  We determined that it was medicating the behavioral issues related to UTI’s, rather then psychotic behavior associated with dementia.  Since Seroquil has black box warnings (death) for the elderly, I was more than pleased to eliminate it.

She had begun having seizures after starting seroquil. a potential side effect even with anti seizure meds.  The pharmaceutical consultation revealed anti seizure meds also cause seizures if doses are missed, late or low dose was taken.  Once on anti seizure meds, one must stay on them.  He warns that it permanently lowers the resistance to seizures, although other pharmacists suggested a slow taper is possible.

The delusional side effects of Dilantin, her original medication, are ill advised for a demented patient.   It took me nearly two and a half years to talk the doctors into letting me try a slow wean off the Dilantin, hoping the fact she had not taken Seroquil for over six months and that her cancer doses of cannabis might stop potential seizures.  Although her cognitive capabilities were notably and significantly improved, she still seized, even with using a slow taper and cannabis.

We next went to Depekote, which gave her diarrhea.  We weaned her slowly, as it is also an antidepressant.  That took nearly three weeks.  The diarrhea kept her in constant battles with UTIs, which tend to promote seizures in demented patients, a vicious downward spiral.  We began feeding her Metamucil cookies.  It seemed like that was all she ate.

We then put her on Lamotragine.  When she seized, the dose was increased…..which gave her diarrhea.  Back to that vicious cycle.  More cookies and holy root balm to rescue her poor little raw butt! I used MU’s recipe with my twist (thanks MU!).

Next we tried Gabapentin, hoping that she would acclimate to the initial drowsiness.  Again she seized on the dose, so we increased the night dose to compensate.  The results were diarrhea….more cookies.

Keppra is well accepted for seizures, but it too gives Mom diarrhea.  Opium tincture is the last choice drug for its control.  Dosing is easier and we have more time and room for nutritious/delicious food.  It was time for closer supervision; she was placed on in home hospice care.  Weekly she gets visits from health care, social and spiritual sectors.

I don’t know what we will try next; perhaps, if Mom had never gone on anti seizure meds (off label for muscle spasms), she would only be on cannabis today.  She has never had seizures until now, nor have there been any record of seizures in our family…ever!  She was given Dilantin for muscle spasms, when western medicine quit prescribing Quinine, deeming it damaging to the body, and seizures are not?  But, perhaps the seizures are caused by Alzheimer’s itself, an unusual but occasional occurrence.

The good and interesting news is, with all of what has been happening to mom, I began a mega dose (two plus grams/day) to try and alter her mood.  We dose her every two hours (or our life is hell).  During that period of time, I increased her dose to between .3 and .5 grams.  That is six or seven doses a day or on the light side, 62 grams per month….more then a cancer cure…in one month.

The results were quite unexpected.  The cognitive changes were unmistakably positive.  She began to interact appropriately, become more animated and loving, and appropriately reactive, choosing short phrases.  In short, her cognitive thinking had improved!  She even played jokes on us. When Dino came to visit; she hugged him and kissed him and said “it’s been so long since I seen you.”  Then demanded another round of hugs and kisses!

Even her doctor, whom does not normally sign for medical cannabis cards, noticed the dramatic improvement, saying, “I wish all my Alzheimer’s patients were on cannabis.  Look at her quality of life!”  She signs Mom’s renewals no questions asked.

Where everyone I know (even those with huge tolerances) would be stupid, asleep or puking on two plus grams of cannabis oil in ten hours; mom has gained cognitive capacity!  Who’d of thought?

I read that CBD’s are the anti seizure cannabinoid, so I grew some plants with balanced THC/CBD to see if they can save Mom from seizures and I can add mitigation of seizures, to the list of ailments for which she no longer takes western medication.  To date, those include asthma, arthritic pain, agitation and anxiety of Alzheimer’s, sleeplessness, blood pressure, and muscle spasms.

Mom lost another ten pounds from diarrhea trying the different western meds, but I have Hippie Chicken hanging and will be extracting her soon.  Hopefully, mom will eat then.  (It has become obvious that high CBD strains induce appetite.  She eats well after anti seizure cannabis medication. Hopefully others can watch that tendency to see if this is an isolated response.)

After getting Mom on the high CBD medications, we took our time weaning her off anti seizure meds, ten days on each reduction, with four total reductions.  She did fine during the reduction, but the balanced CBD cannabis did not give her the needed behavioral change of psychotic effects of THC, so we backed her off to .1 mg per dose in balanced CBD/THC oil and the rest of her cannabis dose in high THC strains.

Once off western anti seizure meds, she faired well for nearly three weeks before she seized, at which time we adjusted the dosing to try and compensate for the lowered level of CBD in her system.  Just prior to bed we gave her a full gram of balanced CBD/THC oil, then again as she slept in the morning such that it would wear off by the time she woke.    Six days later she seized again, so we put her on immediate doses of Lorazapam, then back on Keppra, with liquid Opium to combat the diarrhea.

Next I’d like to try Betane Hydrochloride to aid in digestion for the diarrhea.  Although Mom’s life is limited in length, it would be nice if she did not have to take the opiates.  Updates will follow.

For now, she is on anti seizure meds, opiates for diarrhea, cannabis for asthma, blood pressure, muscle spasms, arthritic pain and sleeplessness, anxiety, aggression of Alzheimer’s.  She weighs 86 pounds at 5’4” now.  She eats and drinks but not enough to sustain.  (Even hippie chicken didn’t work as well as i had hoped.)  But, fourteen years after initial symptoms, she is mostly happy and loving….as long as she gets her cannabis dose!”

http://skunkpharmresearch.com/alzheimers-mom-and-cannabis/

 

Alzheimer’s: Marijuana as Effective Medicine

“Cannabis is getting much positive publicity and seems to be regaining its popularity of one hundred years ago when it was the most widely used drug for about 100 different diseases. There is a big toodoo nowadays about Alzheimers which has turned into almost an epidemic for old folks with some even in their 50’s. So far nobody seems to have put a handle on it and I won’t either.The latest information seems to be that there are senile plaques in the cerebral cortex and subcortical grey matter but whether these plaques are a cause or effect seems to be up for grabs.

I don’t know either. My Merck manual says that four million Americans have it, mostly those over 60 years old. It is a very expensive disease for nursing homes and nursing care probably at least 100 billion dollars per year.

As a Medical Marijuana doctor, I jumped into this fracas when I heard that a lady spouse of an Alzheimers patient went to a Medical Marijuana Advisory Committee meeting of The Oregon Medical Marijuana Program (OMMP) and demanded that her husband be given a permit. She was successful and the medical statistics from OMMP indicate that somewhat less than 50 people have Marijuana permits for this disease. It is called Alzheimers Rage.

The above really didn’t surprise me because there are several Central Nervous System (CNS) diseases for which Cannabis/Marijuana (C/MJ) works very well. These include ALS, Epilepsy, Multiple Sclerosis, Parkinsonism, PTSD and Traumatic Brain Injuries (TBIs). I don’t know if anyone has figured out why C/MJ works for these conditions but why ask if those suffering say that C/MJ works.

Tod Mikiyuria, the foremost scholar in this area, says that C/MJ works as a modulator which is a term of general meaning which possibly just means that it works.

The standard drugs are almost worthless, many seem to be Cholinergics related to Acetyl Choline, the standard Neuro transmitter nerve cell to cell and nerve cell to muscle. At any rate C/MJ seems to work better than any of the heavily advertised drugs.

Cannabis/Marijuana is simultaneously getting much positive publicity and seems to be regaining its popularity of one hundred years ago when it was the most widely used drug for about 100 different diseases.

Those of us advocates for Medical Marijuana who have suffered scorn and derision for DEVIL WEED causing REEFER MADNESS can finally say

WE TOLD YOU SO!!!” –
 
Dr. Phil Leveque 
 

Cannabidiol Reduces Aβ-Induced Neuroinflammation and Promotes Hippocampal Neurogenesis through PPARγ Involvement

“CBD blunted neuroinflammation sustained by astrocytes through PPARγ selective activation in vitro and in vivo.

Results from the present study prove the selective involvement of PPARγ in the anti-inflammatory and neuroprotective effects of CBD here observed either in vitro and in vivo. In addition, CBD significantly promoted neurogenesis in Aβ injured rat hippocampi, much expanding its already wide spectrum of beneficial actions exerted in AD models, a non negligible effect, due to its capability to activate PPARγ.

In conclusion, results of the present research demonstrate that CBD may exert protective functions through a PPARγ dependent activation, which leads to a reduction in reactive gliosis and consequently in neurodegeneration. Moreover, in the current experimental conditions this phytocannabinoid appears to stimulate neurogenesis since it increases DCX immunopositive cell proliferation rate in rat DG.

Innovative therapeutic approaches which could significantly improve AD course require new molecules that will be able to have an impact on different pathological pathways, which converge at the progressive neurological decline. CBD has shown a capability to profoundly reduce reactive astrogliosis and to guarantee both direct and indirect neuronal protection in Aβ induced neuroinflammation/neurodegeration. So far, the lack of understanding of the precise molecular mechanism involved in CBD pharmacological actions, has had limited interest and has puzzled investigators.

Currently, findings of the present study throw some light on the issue, and frame CBD as a new PPARγ activator.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3230631/

Cannabidiol in vivo blunts beta-amyloid induced neuroinflammation by suppressing IL-1beta and iNOS expression.

“Pharmacological inhibition of beta-amyloid (Aβ) induced reactive gliosis may represent a novel rationale to develop drugs able to blunt neuronal damage and slow the course of Alzheimer’s disease (AD). Cannabidiol (CBD), the main non-psychotropic natural cannabinoid, exerts in vitro a combination of neuroprotective effects in different models of Aβ neurotoxicity. The present study, performed in a mouse model of AD-related neuroinflammation, was aimed at confirming in vivo the previously reported antiinflammatory properties of CBD.

Cannabidiol (CBD), the main non-psychotropic component of the glandular hairs of Cannabis sativa, exhibits a plethora of actions including anti-convulsive, sedative, hypnotic, anti-psychotic, anti-nausea, anti-inflammatory and anti-hyperalgesic properties. CBD has been proved to exert in vitro a combination of neuroprotective effects in Aβ-induced neurotoxicity, including anti-oxidant and anti-apoptotic effects, tau protein hyperphosphorylation inhibition through the Wnt pathway, and marked decrease of inducible nitric oxide synthase (iNOS) protein expression and nitrite production in Aβ-challenged differentiated rat neuronal cells.

In spite of the large amount of data describing the significant neuroprotective and anti-inflammatory properties of CBD in vitro, to date no evidence has been provided showing similar effects in vivo. To achieve this, the present study investigated the potential anti-inflammatory effect of CBD in a mouse model of AD-related neuroinflammation induced by the intrahippocampal injection of the human Aβ (1–42) fragment.

The results of the present study confirm in vivo anti-inflammatory actions of CBD, emphasizing the importance of this compound as a novel promising pharmacological tool capable of attenuating Aβ evoked neuroinflammatory responses.

 …on the basis of the present results, CBD, a drug well tolerated in humans, may be regarded as an attractive medical alternative for the treatment of AD, because of its lack of psychoactive and cognitive effects.”

Read more: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2189818/

 

Plants with traditional uses and activities, relevant to the management of Alzheimer’s disease and other cognitive disorders.

“In traditional practices of medicine, numerous plants have been used to treat cognitive disorders, including neurodegenerative diseases such as Alzheimer’s disease (AD) and other memory related disorders. An ethnopharmacological approach has provided leads to identifying potential new drugs from plant sources, including those for memory disorders. There are numerous drugs available in Western medicine that have been directly isolated from plants, or are derived from templates of compounds from plant sources. For example, some alkaloids from plant sources have been investigated for their potential in AD therapy, and are now in clinical use (e.g. galantamine from Galanthus nivalis L. is used in the United Kingdom).

 Various other plant species have shown favourable effects in AD, or pharmacological activities indicating the potential for use in AD therapy.

This article reviews some of the plants and their active constituents that have been used in traditional medicine, including Ayurvedic, Chinese, European and Japanese medicine, for their reputed cognitive-enhancing and antidementia effects. Plants and their constituents with pharmacological activities that may be relevant to the treatment of cognitive disorders, including enhancement of cholinergic function in the central nervous system, anti-cholinesterase (anti-ChE), antiinflammatory, antioxidant and oestrogenic effects, are discussed.”

http://www.ncbi.nlm.nih.gov/pubmed/12557240

Smoked Medicinal Cannabis for Neuropathic Pain in HIV: A Randomized, Crossover Clinical Trial.

“In 1999, a report of the United States Institute of Medicine recommended further investigations of the possible benefits of cannabis (marijuana) as a medicinal agent for a variety of conditions, including neuropathic pain due to HIV distal sensory polyneuropathy (DSPN). The most abundant active ingredient in cannabis, tetrahydro-cannabinol (THC), and its synthetic derivatives, produce effective analgesia in most animal models of pain. The antinociceptive effects of THC are mediated through cannabinoid receptors (CB1, CB2) in the central and peripheral nervous systems, which in turn interact with noradrenergic and κ-opioid systems in the spinal cord to modulate the perception of painful stimuli. The endogenous ligand of CB1, anandamide, itself is an effective antinociceptive agent. In open-label clinical trials and one recent controlled trial, medicinal cannabis has shown preliminary efficacy in relieving neuropathic pain.”

“We conducted a clinical trial to assess the impact of smoked cannabis on neuropathic pain in HIV. This was a phase II, double-blind, placebo-controlled, crossover trial of analgesia with smoked cannabis in HIV-associated distal sensory predominant polyneuropathy (DSPN).”

 “…pain relief was greater with cannabis than placebo…”

 “Smoked cannabis was generally well tolerated and effective when added to concomitant analgesic therapy in patients with medically refractory pain due to HIV DSPN.”

“Our findings suggest that cannabinoid therapy may be an effective option for pain relief in patients with medically intractable pain due to HIV-associated DSPN.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3066045/

Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis.

“Central pain in multiple sclerosis (MS) is common and often refractory to treatment…

We conducted a single-center, 5-week (1-week run-in, 4-week treatment), randomized, double-blind, placebo-controlled, parallel-group trial in 66 patients with MS and central pain states (59 dysesthetic, seven painful spasms) of a whole-plant cannabis-based medicine (CBM), containing delta-9-tetrahydrocannabinol:cannabidiol (THC:CBD) delivered via an oromucosal spray, as adjunctive analgesic treatment…

CONCLUSIONS:

Cannabis-based medicine is effective in reducing pain and sleep disturbance in patients with multiple sclerosis related central neuropathic pain and is mostly well tolerated.”

http://www.ncbi.nlm.nih.gov/pubmed/16186518

Randomized controlled trial of cannabis-based medicine in spasticity caused by multiple sclerosis.

Abstract

“Symptoms relating to spasticity are common in multiple sclerosis (MS) and can be difficult to treat. We have investigated the efficacy, safety and tolerability of a standardized oromucosal whole plant cannabis-based medicine (CBM) containing delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD), upon spasticity in MS. A total of 189 subjects with definite MS and spasticity were randomized to receive daily doses of active preparation (n = 124) or placebo (n = 65) in a double blind study over 6 weeks. The primary endpoint was the change in a daily subject-recorded Numerical Rating Scale of spasticity. Secondary endpoints included a measure of spasticity (Ashworth Score) and a subjective measure of spasm. The primary efficacy analysis on the intention to treat (ITT) population (n = 184) showed the active preparation to be significantly superior (P = 0.048). Secondary efficacy measures were all in favour of active preparation but did not achieve statistical significance. The responder analysis favoured active preparation, 40% of subjects achieved >30% benefit (P = 0.014). Eight withdrawals were attributed to adverse events (AEs); six were on active preparation and two on placebo. We conclude that this CBM may represent a useful new agent for treatment of the symptomatic relief of spasticity in MS.”

http://www.ncbi.nlm.nih.gov/pubmed/17355549

Clinical efficacy and effectiveness of Sativex, a combined cannabinoid medicine, in multiple sclerosis-related spasticity.

Abstract

“Multiple sclerosis (MS) is associated with a wide range of disease symptoms and amongst these, spasticity is one of the most disabling and has the greatest impact on patient well-being and quality of life. Until now, available drug therapies for spasticity appear to have limited benefit and are often associated with poor tolerability. In a recent Spanish survey it was noted that multidrug therapy and a low control rate were common features for a large proportion of patients with MS-related spasticity, suggesting that currently available monotherapies lack significant activity. Sativex is a 1:1 mixture of δ-9-tetrahydrocannabinol and cannabidiol derived from Cannabis sativa chemovars, which is available as an oromucosal spray. Clinical experience with Sativex in patients with MS-related spasticity is steadily accumulating. Results from randomized, controlled trials have reported a reduction in the severity of symptoms associated with spasticity, leading to a better ability to perform daily activities and an improved perception of patients and their carers regarding functional status. These are highly encouraging findings that provide some much needed optimism for the treatment of this disabling and often painful symptom of MS.”

http://www.ncbi.nlm.nih.gov/pubmed/22509985