cannabis and pmdd

Cannabis: Use in PMDD and other Related Disorders

Leslie Reyes, BA, RN, ACNA Secretary, Board of Directors, Executive Committee

Marcie Cooper, MSN, RN, AHN-BC, ACNA Board of Directors

American Cannabis Nurses Association

Copyright 2014, All Rights Reserved

Cannabis: Caregiver Information…

Basic Information Patients and Caregivers Should Know about Cannabis:1. The Endocannabinoid System: How does cannabis really affect the human body?2. THC vs. CBD, or “Sativa” vs. “Indica”: What are the main strains of cannabis and how do

we chose the appropriate one?3. What are the different delivery systems available and what are the standard dosing

recommendations?4. How do we “titrate” the dose?5. Is cannabis safe? Is it addictive? Will it impair me? Does cannabis use lead to mental

illness or addiction?6. Will smoking cannabis cause lung cancer or COPD?7. What happens if someone “overdoses” on cannabis?8. How does cannabis “treat” PMDD and other issues during the Menstrual Cycle?9. How does Hemp Oil differ from “CBD (cannabidiol-only)” oil?10. Why all the politics surrounding cannabis?

Leslie Reyes, BA, RN American Cannabis Nurses Association copyright 2014. All rights reserved.

Some important information about cannabis and the human endocannabinoid system…

!What is the Human Endocannabinoid System?

!What are cannabinoids?

!Indica vs. Sativa or THC vs. CBD


What Is The Endocannabinoid System?From Dustin Sulak, DO, NORML 2015

! The human endocannabinoid system (ECS) is a system of neurotransmitters and receptors throughout the body which promotes health and homeostasis. The endocannabinoid system is a group of neuromodulatory lipids and their receptors in the brain that are involved in a variety of physiological processes including appetite, pain-sensation, mood, and memory.

! The ECS may be the most important physiologic system involved in maintaining health and homeostasis (the maintenance of a stable, balanced, internal environment despite fluctuations in the external environment).

! The ECS, made up of Endocannabinoids and their receptors, are found throughout the body: in the brain, the major organs (heart, pancreas, liver), connective tissues, glands, and immune cells. In each tissue, the cannabinoid system performs different tasks, but goal, again, is homeostasis.


What is the “Entourage Effect”?

!Cannabinoids do not work as well when synthesized and isolated.

!For instance, CBD is not fully activated medicinally without some THC, and THC is not as effective without some CBD.

!Full plant extractions or full plant based medicines are the most effective

!When the cannabinoids of the cannabis plant work together, this is known as “The Entourage Effect”.


What are Cannabinoid Receptors? ! Cannabinoid receptors are present throughout the body, and are believed to

be more numerous than any other receptor system. Researchers have identified two main cannabinoid receptors:

! CB1, predominantly present in the nervous system, connective tissues, gonads, glands, and organs; and

! CB2, predominantly found in the immune system and its associated structures.

! Many tissues contain both CB1 and CB2 receptors, each linked to a different action. Researchers speculate there may be a third cannabinoid receptor waiting to be discovered.


What are Endocannabinoids?

Endocannabinoids are the substances our bodies naturally make to stimulate these receptors. The two most well understood of these molecules are called:

! Anandamide (from the Indian word “Ananda=Bliss”) and

! 2-arachidonoylglycerol (2-AG).


What are Cannabinoids?

! What are Cannabinoids? Or “Phytocannabinoids”?

! Cannabinoids, the active compounds found in the cannabis plant, promote homeostasis at every level of biological life, from the sub-cellular, to the entire organism. These are the compounds which bind to the cannabinoid receptors in the human cannabinoid system.

! There are over 66 compounds in the cannabis plant. The two cannabinoids every health care professional should know about

! “Delta-9 Tetrahydrocannabidiol (THC) and

! “Cannabidiol” (CBD)


THC vs. CBD or “Indica vs. Sativa”! The two main cannabinoids to know about are THC and CBD

! The two main strains of cannabis are Sativa (THC-dominant) and Indica (CBD-dominant)

! THC “Delta-9 Tetrahydrocannabinol”: “Sativa Dominant Strains” THC “Stimulates.”

! Psychoactive, Anti-depressant, Appetite-Stimulant, Anti-Neoplastic (kills cancer cells), Anti-Tumor, Analgesic, anti-emetic (nausea).

! CBD “Cannabidiol”: “Indica Dominant Strains” CBD “Sedates.”

! Analgeic, neuroprotectant, anti-psychotic (the “opposite” of THC, CBD can be used if a patient has “overdosed” on a high THC strain or preparation), anti-proliferative (inhibits cancer cell growth)


Cannabis can be used as an…

✓ Analgesic

✓ Anti-inflammatory

✓ Anti-emetic

✓ Appetite stimulant

✓ Anti-neoplastic

✓ Neuroprotectant ✓ Anti-spasmodic

✓ Anti-oxidant

✓ Anti-insomnia

✓ Anxiolytic

✓ Anti-depressant

✓ Anti-epiletic ✓ Bone stimulant


Delivery systems: In what forms can a patient take cannabis? Inhaled: Vaporized, Smoked

! Dried Flowers: “Joint” cigarettes, Water pipes “bongs”, pipes, vaporization machines, vaporizer pens

! Oils and extractions (hash, trichrome) can be inhaled: E-cigarettes, oil-vaporizers

Ingested:Edibles, pills, oils

Absorbed:

! Suppositories, topicals (lotions and oils on the skin), tinctures (under the tongue)

Cannabis cannot be injected or administered via IV.


What are the benefits of inhaled vs. edible cannabis?

Inhaled (vaporized or smoked):

! Benefits: Easy for the patient to self-titrate the dose, Use minimum dosage for maximum effects, Difficult to overdose, no evidence of permanent lung damage, no risk of lung cancer

! Drawbacks: Bronchial irritation and infection, odor from smoke/vapor, dry cough, shorter duration of action

Edible or ingested:

! Benefits: No irritation to lungs or respiratory tract, longer duration of action! Drawbacks: Hard to titrate, easy to “overdose”, unpleasant side effects if taken

too much, expensive (need more plant material when ingesting than if inhaling)


Hempseed Oil vs.“Cannabidiol/CBD” Oil: Is there a difference? And if so, what is it?

! Hempseed oil should not be confused with a Cannabidiol/CBD oil extraction.! Hempseed oil has proven nutritional qualities and comes from the Hemp Plant, which is not the

same as the Cannabis plant.! However, Hempseed oil's benefits do not come from the trace amounts of CBD found in the oil,

but rather, the eight proteins found in the plant and essential fatty acids which are also in the plant.

! Using isolated CBD extractions has not been proven effective as a medicine to control seizures or other illnesses, and it does not work well without the other cannabinoids, including THC.

! It is important to use full plant extractions! According to peer reviewed reports, Hempseed oil contains very little CBD, has no medicinal

effect (though it may have nutritional qualities), and is not the same thing as CBD oil. Though there are conflicting reports, and some say there could be up to 50% Cannabidiol in natural hempseed oil, but without any THC in hemp oil, the CBD is not activated. More research is needed.

! References: http://www.chrisconrad.com/pdf/cannayieldsdosage10.pdf


Delivery Systems and Dosing/Administration…

! Cannabis can be:

! Inhaled: Smoke or Vaporization! Ingested: Edibles or Pill, raw plant “juicing”! Absorbed: Tinctures (Sublingual) or Salves (topicals)! Cannabis cannot be taken via IV or injection

! The method of administration varies from patient to patient and condition.


Delivery System Methods! Inhalation: Vaporized or Smoked Cannabis.

! Onset of Action: 15 minutes

! Duration: 2-3 hours

! Benefits: Easy to titrate (or determine minimal effective dosage), need less medicine to control symptoms, no risk of permanent lung damage, low risk of “overdose”.

! Risks: Increase in respiratory tract infections, coughing, elevated heart rate from initial dose.

! Oral: ! Pills and Edibles:

! Onset of Action: 1-3 hours depending on metabolism

! Duration: 5 hours or more ! Benefits: No smoke or vapor, no odor, no respiratory tract irritation

! Risks: Slow onset leads to accidental “overdose”, hard to titrate dose, the same dose and medicine could have different effects on the same patient depending on the patient’s metabolism at that time.

!  Sublingual, Tinctures and Sprays:

! Onset of Action: 5-30 minutes

! Duration: 3-5 hours or more

! Benefits: Quicker onset than edibles and pills. Easier to titrate than edibles and pills.

! Risks: Easier to “overdose” than with inhaled preparation. Slower onset than inhaled preparations. Irritation to mucosal tissues if made with alcohol.


Delivery System Methods (continued)

! Raw Plant “Juicing”: Non-psychoactive, nutritional, preventative.! High in Amino Acids (over 20 varieties)! High in Omega 3 and Omega 6 ! More nutritional than medicinal, but still have preventative

properties.! Healing properties: Still need more information and studies, but

juicing raw cannabis leaves is highly nutritional.! Topical (Patches, Salves, Lotions):

! Onset of Action: 1-3 minutes! Duration: 3-5 Hours! Note: Patches can be left on for 24 hours


Delivery Options: Smoked cannabis has been found to be relatively safe and does not cause permanent lung disease. Smoking makes titrating the dosage easy and allows the patient to control the dosage. However, not everyone is comfortable or able to inhale smoked cannabis, and most hospitals are smoke-free.

Delivery options which would be appropriate in the healthcare setting:-Vaporization -Extractions and Tinctures-Edibles/teas -Elixirs-Pills/supplementsPhoto: A nurse helps a patient to inhale cannabis fumes from a vaporizer at an Israeli nursing home on March 9, 2011. Together with Israel's health ministry, the Tikon Olam company currently is distributing cannabis for medicinal purposes to more than 1,800 people in Israel.


Uriel Sinai/Getty Images.

Dosage and Administration

! Donald Abrams, MD: Professor of Clinical Medicine at the University of California, San Francisco

! Research paper "Medical Cannabis: Rational Guidelines for Dosing," published Jan. 2004:

! “An experienced cannabis smoker can titrate and regulate dose to obtain the desired acute effects and to minimize undesired effects. Each puff delivers a discrete dose of cannabinoids to the body. Puff and inhalation volume changes with phase of smoking, tending to be highest at the beginning and lowest at the end of smoking a cigarette...

! “Oral ingestion of THC or cannabis has quite different pharmacokinetics than inhalation. The onset of action is delayed and titration of dosing is more difficult...”

! “Thus, a patient-determined, self-titrated dosing model is recommended.” ! “This self-titration model is acceptable given the heretofore-discussed variables as

well as the low toxicity of cannabis.” ! “This construct is not unique to cannabis. Many other drugs have relatively low toxicity

and high dosing ceilings (gabapentin being one notable example, insulin on a sliding scale another example), and are titrated to effect."


Titrating the Dose

Start Low and Go Slow!!

! Average Starting Dose: 2.5 mg-10 mg THC (see “Edibles Education”)! THC is relatively safe and has NOT been found to interact negatively with other

medications.! Inhalation is the easiest way to control the dosage. Long term clinical studies

have shown that inhaled cannabis, even in heavy users, does not lead to an increase in permanent lung disease. Using cannabis does not lead to COPD. Heavy cannabis use is not associated with head, neck or lung cancers, even when smoked and inhaled.

! When using edibles, start with the lowest dosage, wait a half hour before taking more. The onset is very slow when ingesting pills or edibles and patients often end up taking too much when an effect is not felt within 15 minutes.


“Final Dosing Recommendations" Based on Dr. Abrams’ Research:

Strength of Cannabis(THC)

Daily dosage of cannabis corresponding to 2.5 - 90 mg of THC

10% THC .15 g . 5.55g

15% THC .12 g . 3.69g

20% THC .08 g . 2.79g

25% THC .04 g . 2.25g

30% THC .01 g . 1.86g

Note: When using edibles/ingestibles, always start with the lowest dosage possible (2.5 mg preferred) and wait at least a half hour before taking another dose. It can take up to 1-2 hours to metabolize edible cannabis.

The “average” patient may use the equivalent of 1-2 grams of dried flower cannabis per day, equivalent to about 2.5-10 mg of THC, depending on the plants THC % content.


Can One Overdose and Die from too much Cannabis? Answer: NO

There has never been a death in recorded history due to overconsumption of Cannabis!

No Marijuana Deaths in 2 Large Studies (Summary published on WebMD)


✓Is Cannabis Safe? The ACTUAL potential side effects of Cannabis…-Confusion -Euphoria -Drowsiness -Strange dreams-Paranoia -Panic-induced increased heart rate/pulse -Dry Mouth -Susceptibility to bronchitis when smoked-Red Eyes -Legal issues/Urine Drug Screens Leslie Reyes, BA, RN American Cannabis Nurses Association copyright 2014. All rights reserved.

What happens if someone “overdoses”?! It is very hard to overdose on inhaled (smoked or vaporized) cannabis. There is no amount of cannabis which is lethal to humans.! The symptoms of “overdose” are:

! Paranoia and disorientation! Anxiety! Elevated heart rate! Extreme sleepiness/heaviness! Dizziness! Nausea

! If “paranoia” or overdose symptoms occur:! Note the strain and delivery system! How much was used in what period of time?! If ingested, when was the last time the patient ate and what did they eat?

! Fats and Caffeine can have an effect on the psychoactive effects of THC

! Have patient drink lots of water and relax in a quiet place.! Remind patient that the effects are temporary, non-damaging, and non-lethal, and that the effects will usually wear off within 1-2 hours.! Please note, the addictive properties of cannabis are very low, and withdrawal symptoms usually last 1-2 weeks and are similar to

caffeine withdrawals.


PMDD and Cannabis Use Throughout the Menstrual Cycle…

! Common Medications Used for PMDD:

! SSRI’s/Antidepressants: ! Can take up to two weeks to start working, which makes them a poor option for the patient

suffering from PMDD! SSRI’s have withdrawal symptoms, but are inappropriate to take during the cycle when

PMDD symptoms are normally not present

! Anxiolytics/Anti-Anxiety Medications! Xanax, Ativan, Klonopin

! Hormones:! Birth Control Pills! Other synthetic Hormones


PMDD and Cannabis Use Throughout the Menstrual Cycle…

! Treatments for PMS and PMDD typically include pain killers, muscle relaxants and anti-depressants.

! Anti-depressants can take several days to a couple weeks to become effective, making them a less than ideal option for a condition which lasts several days once a month.

! Cannabis helps these symptoms immediately, much sooner than pain killers and muscle relaxants will begin to take effect.

! Additionally, there is no evidence that cannabis is physically addictive, and it is very easy for the patient to titrate the dosage

! The patient can use cannabis only when needed. It is the only medication we are aware of that can be used p.r.n.=as needed.


Lung Cancer and Heavy Cannabis Smoking

! Donald Tashkin, Pulmonologist at the University of California at Los Angeles: Studied marijuana for 30 years.

! The study was actually suggestive of cannabis having protective properties against cancer. This study is relevant, because although when looked under a microscope, a “burned joint” contains more carcinogens than a tobacco cigarette, it implies that THC has protective qualities cancer cells.


Misconceptions about THC…

! THC is the “dangerous” part of cannabis = FALSE! There have been no human deaths attributed to an overdose in THC.! Marinol (Generic name: Dronabinol), is a legal medication which consists of 100%

synthetic THC and very few reported deaths reported in the 30+ years it has been on the market.

! Even in high-CBD strains used to control seizures in children contain some THC.! The THC is necessary for the other cannabinoids to work.

! Isolating and synthesizing cannabinoids is good medicine = FALSE! See Above!

Link to video where Sanjay Gupta outlines the “Entourage Effect”: http://www.cnn.com/2014/03/11/health/gupta-marijuana-entourage/


http://www.cnn.com/2014/03/11/health/gupta-marijuana-entourage/

Misconceptions about cannabis’ connection to mental illness and addiction

! Cannabis causes schizophrenia and other psychiatric disorders = FALSE

! Research at Harvard Medical School and VA Boston Healthcare concluded that “…having an increased familial risk for schizophrenia is the underlying basis for schizophrenia — not cannabis use.”

! Researchers led by Markus Leweke of the University of Cologne in Germany studied 39 people with schizophrenia. At the end of the four-week trial, there was no difference between those getting CBD or the pharmaceutical psychiatric medication and both groups showed improvement.

! Data was collected over nine years from psychiatric patients at a Long Island hospital for a larger cohort study. All of the patients used for this study fit the DSM-IV requirements for bipolar I disorder.

! Patients with bipolar disorder demonstrated significantly higher neurocognitive performance when they also had a history of cannabis dependence.

! These results along with the schizophrenia studies suggest that marijuana use improves the cognitive functioning of patients with severe psychiatric disorders.


Various medicinal applications of cannabis…1. Analgesic/Pain Management ! Neuropathic pain/Chronic pain related to disease process. (THC: analgesic)

! -Relieves neuropathic pain Associated with diabetes, cancer, multiple sclerosis, and HIV

! -Relieves chronic Injury-related pain (musculoskeletal injury)! Note: Adding a cannabinoid to opioid therapy may lead to greater pain relief at

lower opioid doses. 2. Anti-bacterial/Immuno-stimulant/Anti-inflammatory (Nursing Diagnosis: Infection/Risk for Infection, Inflammatory response)

! Immune disorders (Limonene: Stimulates immune system)! Infections (CBD, CBGA, CBG: slows the growth of bacteria)! Reduces inflammation (CBD, CBGA: anti-inflammatory)


Why aren’t there more doctors and nurses talking about cannabis with their patients? Schedule I Drugs are defined as:

Drugs with no currently accepted medical use and a high potential for abuse. Schedule I drugs are considered the most dangerous drugs of all the drug schedules with potentially severe psychological or physical dependence.

Some examples of drugs currently listed as Schedule I are:

Heroin, lysergic acid diethylamide (LSD), MDMA or 3,4-methylenedioxymethamphetamine (ecstasy), methaqualone, psilobycin “psychedelic” mushrooms, peyote…

….and Cannabis.

http://www.justice.gov/dea/druginfo/ds.shtml


http://www.justice.gov/dea/druginfo/ds.shtml

The American Cannabis Nurses Association supports: The removal of Cannabis from Schedule I classification.The Use of the Entire natural cannabis plant as medicine, both high THC/CBD and low THC/CBD strains.The Education of Health Care providers on the science of Cannabis and the Endocannabinoid system


• Hajrasouliha AR, Tavakoli S, Ghasemi M, Jabehdar-Maralani P, Sadeghipour H, Ebrahimi F & Dehpour AR. (2008). Endogenous cannabinoids contribute to remote ischemic preconditioning via cannabinoid CB2 receptors in the rat heart. European Journal of Pharmacology. 579:246-52.

• Hiley CR. (2009). Endocannabinoids and the heart. Journal of Cardiovascular Pharmacology. 0(0):1-10.

• Hohmann AG, Suplita RL, Bolton NM, Neely MH, Fegley D, Mangieri R, Krey JF, Walker JM, Holmes PV, Crystal JD, Duranti A, Tontini A, Mor M, Tarzia G & Piomelli D. (2005). An endocannabinoid mechanism for stress-induced analgesia

• Idris et al (2005). Regulation of bone mass, bone loss and osteoclast activity by cannabinoid receptors. Nature Medicine. 11:774-9.

• Itai B. (2007). Regulation of skeletal remodeling by the endocannabinoid system. Annals of the New York Academy of Sciences.

• Kress M & Kuner R. (2009). Mode of action of cannabinoids on nociceptive nerve endings. Exp. Brain Res. Doi 10.1007/s00221-009-1762-0

• Lever IJ, Robinson M, Cibelli M, Paule C, Santha P, Yee L, Hunt SP, Cravatt BF, Elphick MR, Nagy I & Rice ASC. (2009). Localization of the endocannabinoid-degrading enzyme fatty acid amide hydrolase in rat dorsal root ganglion cells and its regulation after peripheral nerve injury. The Journal of Neuroscience. 29(12): 3766-80.

• Mach, R., Montecucco, F. & Steffens, S. (2008). Cannabinoid receptors in acute and chronic complications of atherosclerosis. British Journal of Pharmacology. 153: 290-298.

• Marsicano G, Wotjak CT, Azad SC, Bisogno T, Rammes G, Cascio MG, Hermann H, Tang J, Hofmann C, Zieglgänsberger, Di Marzo V & Lutz B. (2002). The endogenous cannabinoid system controls extinction of aversive memories. Nature. 418:530-4.

Additional Reading


Additional Reading• Antineoplastic activity of cannabinoids:http://www.ncbi.nlm.nih.gov/pubmed/1159836

• Ofek et al (2006). Peripheral cannabinoid receptor, CB2, regulates bone mass. Proceedings of the National Academy of Sciences of the United States of America. 103:696-701.

• Pacher P & Steffens S. (2009). The emerging role of the endocannabinoid system in cardiovascular disease. Semin Immunopathol. doi 10.1007/s00281-009-0145-8

• Palazuelos, J., Davoust, N., Julien, B., Hatterer, E., Aguado, T., Mechoulam, R., Benito, C., Romero, J., Silva, A., Guzmán, M., Nataf, S. & Galve-Roperh, I. (2008). The CB2 cannabinoid receptor controls myeloid progenitor trafficking. The Journal of Biological Chemistry. 283(19): 13320-13329.

• Panikashvile D, Mechoulam R, Beni SM, Alexandrovich A & Shohami E. (2005). CB1 cannabinoid receptors are involved in neuroprotection via NF-?B inhibition. Journal of Cerebral Blood Flow & Metabolism. 25: 477-84.

• Pertwee, R. G. (2004). Receptors and pharmacodynamics:natural and synthetic cannabinoids and endocannabinoids. In G. W. Guy, B. A. Whittle & P. Robson (Eds.), Medicinal uses of cannabis and cannabinoids. (pp. 103-140). London: Pharmaceutical Press.

• Pertwee, R. G. (2005). The therapeutic potential of drugs that target cannabinoid receptors or modulate the tissue levels or actions of endocannabinoids. Aaps J, 7(3), E625-654.

• Pertwee, R. G. (2006). Cannabinoid pharmacology: the first 66 years. Br J Pharmacol, 147 Suppl 1, S163-171.

• Sagredo, O., Garcia-Arencibia, M., de Lago, E., Finette, S., Decio, A. & Fernandez-Ruiz, J. (2007). Cannabinoids and neuroprotection in basal ganglia disorders. Molecular Neurobiology. 36: 82-91.

• Sarzani R. (2008). Endocannabinoids, blood pressure and the human heart. Journal of Neuroendocrinology. 20(Suppl.1):58-62.

• Shouman B, Fontaine RH, Baud O, Schwendimann L, Keller M, et.al. (2006). Endocannabinoids potently protect the newborn brain against AMPA-kainate receptor-mediated excitotoxic damage. Br J Pharmacol., 148(4), 442-51.


References• Aggarwal, S. K., Carter, G. T., Sullivan, M. D., ZumBrunnen, C., Morril, R., & Mayer, J. A. (2009). Medicinal use of cannabis in the United

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• American Herbal Pharmacopoeia (2013). Cannabis Inflorescence: Standards of Identity, Analysis, and Quality Control. Scotts Valley, CA: American Herbal Pharmacopoeia.

• Grotenhermen, F. & Russo, E. (Eds.) (2002). Cannabis and Cannabinoids: Pharmacology, Toxicology, and Therapeutic Potential. NY: The Haworth Integrative Healing Press, Inc.

• Izzo AA, Borrelli F, Capasso R, Di Marzo V & Mechoulam R. (2009). Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb. Trends in Pharmacological Sciences. 30(10):515-27.

• Joy, J.E., Watson, S.J. & Benson, J.A. (1999). Marijuana and Medicine: Assessing the Science Base. Washington, DC: National Academy Press (Institute of Medicine). ISBN 0-309-07155-0

• Mathre, ML (1997). Cannabis in Medical Practice: A Legal, Historical and Pharmacological Overview

• Dreher, M., PhD. et al. (1997), “Prenatal Marijuana Exposure and Neonatal Outcomes in Jamaica: An Ethnographic Study” Pediatrics, February 1994, Volume 93, Number 2, pp. 254-260. American Academy of Pediatrics.

• Tashkin, D., et al. (2006), "Marijuana use and the risk of lung and upper aerodigestive tract cancers: results of a population-based case-control study." Cancer Epidemiology Biomarkers & Prevention 15.10 (2006): 1829-1834.

• Guzman, M. (2006) “Cannabinoids: potential antitumoral agents?” Department of Biochemistry and Molecular Biology, Complutense University, Madrid Spain. Drug Alcohol Depend. 1986 Oct;18(2):213-24.

• Sulak, Dustin (2015) “Introduction to the Endocannabinoid System” by Dustin Sulak, DO, Integr8 Health, NORML.org http://norml.org/library/item/introduction-to-the-endocannabinoid-system February, 2015

• Schwartz, Rose (2011) “Cannabis brings relief to women suffering from PMS and PMDD symptoms” examiner.com


http://norml.org/library/item/introduction-to-the-endocannabinoid-system

http://norml.org/library/item/introduction-to-the-endocannabinoid-system

http://examiner.com

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cannabis and pmdd

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