Involvement of 5HT1A receptors in the anxiolytic-like effects of cannabidiol injected into the dorsolateral periaqueductal gray of rats.

“Cannabidiol (CBD) is a non-psychotomimetic constituent of Cannabis sativa plant that induces anxiolytic effects… In addition, since CBD has been shown to inhibit anandamide metabolism, CB1 receptors could also be involved in the effects of this cannabinoid…

CBD injected into the dorsolateral periaqueductal gray (dlPAG) produced anxiolytic-like effects… The anxiolytic effect of CBD was confirmed in the  Vogel conflict test (VCT)…

CONCLUSION:

These results suggest the CBD interacts with 5HT1A receptors to produce anxiolytic effects in the dlPAG.”

http://www.ncbi.nlm.nih.gov/pubmed/18446323

Cannabidiol blocks long-lasting behavioral consequences of predator threat stress: possible involvement of 5HT1A receptors.

“Posttraumatic stress disorder (PTSD) is an incapacitating syndrome that follows a traumatic experience. Predator exposure promotes long-lasting anxiogenic effect in rodents, an effect related to symptoms found in PTSD patients. Cannabidiol (CBD) is a non-psychotomimetic component of Cannabis sativa with anxiolytic effects. The present study investigated the anti-anxiety actions of CBD administration in a model of PTSD…

 Repeated administration of CBD prevented long-lasting anxiogenic effects promoted by a single predator exposure…

 In conclusion, predator exposure promotes long-lasting up-regulation of 5HT1A receptor gene expression in the hippocampus and frontal cortex. Repeated CBD administration prevents the long-lasting anxiogenic effects observed after predator exposure probably by facilitating 5HT1A receptors neurotransmission.

Our results suggest that CBD has beneficial potential for PTSD treatment and that 5HT1A receptors could be a therapeutic target in this disorder.”

http://www.ncbi.nlm.nih.gov/pubmed/22979992

Mitigation of post-traumatic stress symptoms by Cannabis resin: a review of the clinical and neurobiological evidence.

“It is known from clinical studies that some patients attempt to cope with the symptoms of post-traumatic stress disorder (PTSD) by using recreational drugs. This review presents a case report of a 19-year-old male patient with a spectrum of severe PTSD symptoms, such as intense flashbacks, panic attacks, and self-mutilation, who discovered that some of his major symptoms were dramatically reduced by smoking cannabis resin. The major part of this review is concerned with the clinical and preclinical neurobiological evidence in order to offer a potential explanation of these effects on symptom reduction in PTSD.

This review shows that recent studies provided supporting evidence that PTSD patients may be able to cope with their symptoms by using cannabis products. Cannabis may dampen the strength or emotional impact of traumatic memories through synergistic mechanisms that might make it easier for people with PTSD to rest or sleep and to feel less anxious and less involved with flashback memories.

The presence of endocannabinoid signalling systems within stress-sensitive nuclei of the hypothalamus, as well as upstream limbic structures (amygdala), point to the significance of this system for the regulation of neuroendocrine and behavioural responses to stress.

 Evidence is increasingly accumulating that cannabinoids might play a role in fear extinction and antidepressive effects. It is concluded that further studies are warranted in order to evaluate the therapeutic potential of cannabinoids in PTSD.”

http://www.ncbi.nlm.nih.gov/pubmed/22736575

Anxiolytic-like effect of cannabidiol in the rat Vogel conflict test.

“Cannabidiol (CBD) is a major constituent of the Cannabis sativa plant. It inhibits the anxiogenic activity of high doses of Delta9-tetrahydrocannabinol and induces anxiolytic-like effects. However, the mechanisms underlying the actions of CBD are unknown. Therefore, the aim of the present study was to test the effects of CBD in the Vogel test, a widely used animal model of anxiety. 

 In conclusion, CBD induced an anticonflict effect not mediated by benzodiazepine receptors or by non-specific drug interference on nociceptive threshold or water consumption.

These results reinforce the hypothesis that this cannabinoid has anxiolytic properties.”

http://www.ncbi.nlm.nih.gov/pubmed/16876926

The anxiolytic effect of cannabidiol on chronically stressed mice depends on hippocampal neurogenesis: involvement of the endocannabinoid system.

“Cannabidiol (CBD), the main non-psychotomimetic component of the plant Cannabis sativa, exerts therapeutically promising effects on human mental health such as inhibition of psychosis, anxiety and depression. However, the mechanistic bases of CBD action are unclear. Here we investigate the potential involvement of hippocampal neurogenesis in the anxiolytic effect of CBD in mice subjected to 14 d chronic unpredictable stress (CUS). Repeated administration of CBD (30 mg/kg i.p., 2 h after each daily stressor) increased hippocampal progenitor proliferation and neurogenesis in wild-type mice. Ganciclovir administration to GFAP-thymidine kinase (GFAP-TK) transgenic mice, which express thymidine kinase in adult neural progenitor cells, abrogated CBD-induced hippocampal neurogenesis. CBD administration prevented the anxiogenic effect of CUS in wild type but not in GFAP-TK mice as evidenced in the novelty suppressed feeding test and the elevated plus maze. This anxiolytic effect of CBD involved the participation of the CB1 cannabinoid receptor, as CBD administration increased hippocampal anandamide levels and administration of the CB1-selective antagonist AM251 prevented CBD actions. Studies conducted with hippocampal progenitor cells in culture showed that CBD promotes progenitor proliferation and cell cycle progression and mimics the proliferative effect of CB1 and CB2 cannabinoid receptor activation. Moreover, antagonists of these two receptors or endocannabinoid depletion by fatty acid amide hydrolase overexpression prevented CBD-induced cell proliferation.

 These findings support that the anxiolytic effect of chronic CBD administration in stressed mice depends on its proneurogenic action in the adult hippocampus by facilitating endocannabinoid-mediated signalling.”

http://www.ncbi.nlm.nih.gov/pubmed/23298518

Cannabidiol: an overview of some chemical and pharmacological aspects. Part I: chemical aspects.

“Over the last few years considerable attention has focused on cannabidiol (CBD), a major non-psychotropic constituent of Cannabis. In Part I of this review we present a condensed survey of the chemistry of CBD; in Part II, to be published later, we shall discuss the anti-convulsive, anti-anxiety, anti-psychotic, anti-nausea and anti-rheumatoid arthritic properties of CBD. CBD does not bind to the known cannabinoid receptors and its mechanism of action is yet unknown. In Part II we shall also present evidence that it is conceivable that, in part at least, its effects are due to its recently discovered inhibition of anandamide uptake and hydrolysis and to its anti-oxidative effect.”

http://www.ncbi.nlm.nih.gov/pubmed/12505688

http://www.scribd.com/doc/52920296/Cannabidiol-an-Overview-of-Some-Chemical-and-Pharmacological-Aspects-Part-I-Chemical-Aspects

Pot Stirring – ELLE

“Some are using marijuana as their drug of choice to curb anxiety.”

Marijuana Anxiety Disorders
 

 “A thimbleful is all it takes. After a day’s work, I pinch off a small amount of marijuana and put it in a steel-tooth grinder. The flowers, covered in tiny white diamonds of THC, release a piney scent when crushed. I turn on the TV, and instead of taking a glass of wine with my evening news, I take out my vaporizer and set it on the coffee table.

Outside the walls of my bungalow in Oakland, California, I can hear the rush-hour traffic, but I’ve already changed into my Big Lebowski–style robe and slippers. I tap the ground flakes into a canister that I attach to another piece, this one with a bag on the end, and set both on the vaporizer. I flip the switch, and the bag slowly inflates with plumes of white smoke. Once it’s fully clouded, I attach a mouthpiece to the canister, put this to my lips, and press. On the inhale, the cannabinoids taste like sunned grass. My prescription for anxiety disorder didn’t always begin and end with an herb. But I’ve run through enough pharmaceutical drugs to know that pot dulls my panic better than any pill.”

Read more; http://www.elle.com/beauty/health-fitness/pot-stirring-19727

Marijuana nutrients found to help prevent Alzheimer’s disease

“A study conducted by scientists at Scripps Research Institute in California has found that, contrary to marijuana’s reputation, the ingredients of the drug can actually fight off the memory-impairing effects of Alzheimer’s disease.The researchers found that the active ingredient in marijuana — delta-9-tetrahydrocannabinol, or THC — is responsible for the positive effect, as it can prevent the breakdown of the neurotransmitter acetylcholine even better than commercially marketed prescription drugs.

The study also showed that THC could completely prevent the enzyme acetylcholinesterase (AchE) from forming amyloid plaques, whereas twice as much donepezil and tacrine — the two drugs approved for Alzheimer’s treatment — only reduced such clumping by 22 and 7 percent, respectively, the researchers reported in the journal Molecular Pharmaceutics. This led the scientists to conclude that a more effective Alzheimer’s drug could be developed in the future.”

Read more: http://www.naturalnews.com/020667_Marijuana_Alzheimers_drugs.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/

 

Medical Marijuana as Effective Treatment for Alzheimer’s Disease

“Regular low dose cannabis smoking might keep Alzheimer’s away, according to marijuana research by professor Gary Wenk and associate professor Yannic Marchalant of the Ohio State Department of Psychology. Wenk’s studies show that a low dosage in the morning of a certain cannabinoid, a component in marijuana, reversed memory loss in older rats’ brains. In his study, an experimental group of old rats received a dosage, and a control group of rats did not. The old rats that received the drugs performed better on memory tests, and the drug slowed and prevented brain cell death.”

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“Alzheimer’s is a disease unique to humans…, but rat brains are similar enough to human brains to serve as partial models for humans, Wenk said.

… marijuana is the first substance that has worked on older brains in experiments.”

 

Read more: http://alzheimers-review.blogspot.com/2009/11/medical-marijuana-as-effective.html