Pain Management in Primary Care

Case Presentations

Marijuana

Michael Mangione, MD

Chief of Anesthesia and Director of Pain Service, VA Pittsburgh Health Care System

Co-Chair VISN 4 Pain Management Committee

Nancy Wiedemer, CRNP

Pain Management Coordinator,

Philadelphia VA Medical Center

VISN 4 Pain Management POC

Co-Chair VISN 4 Pain Management Committee

Objectives

• Update on OSI

• Marijuana : What clinicians need to know

• Evidence for and against marijuana as a medicine

• Adverse effects

• Interpreting and responding to urine drug testing results

• Update on where the VA is on medical marijuana policy

• What to say to your patients

OSI Update • Informed Consent for Long-term Opioids for Pain (Imed)

• VISN 4 Action Item: April 3,2015

• Directive: May 6,2015

• Objective: Safety Education on new risks of long-term opioid therapy -> Long-term process in place that meets this objective

• Opioid/BZD review January 2015 completed • Outcomes: only 22.5% concurred with treatment plan

• Awareness that this group of patients would benefit from Naloxone safety kit and

• Coordination of Care between MH & Primary Care

• Next up: >/= 200 to 399 MEDD review (One of the 9 Goals set by the USH for OSI)

• VISN 4 above the national mean with high dose opioids

• Review for safety at high doses and process for addressing high dose opioids

Marijuana • Headed toward legalization

• Medical Marijuana in 23 states (including Delaware and New Jersey)

• Recreational Marijuana: 4 states (Colorado, Wash state, Alaska, Oregon) Decriminalized in some states and cities

• Pressure is mounting for federal legalization of medical marijuana

• US Surgeon General Dr. Vivek Murthy on CBS news 2/4/21015

“ We have some preliminary data showing that for some medical conditions and symptoms that marijuana can be helpful.”

• Then later the same day a statement from Department of Health & Human Services: “While clinical trials for certain components of marijuana appear promising for some medical conditions, neither the FDA or the IOM have found smoked marijuana to meet the standards for safe, effective medicine for any condition to date.”

Confusion and Uncertainty • Conflict between State and Federal law

• Ethical, Legal and Policy dilemmas face VA Administration and Practitioners

• Polarized Opinions: Political- Scientific- Moral- Social Attitudes • Review of literature and lectures on Marijuana reflect the opinion of the

author/presenter

• Clinicians may need to identify & address potential health risks due to recreational/illegal use and answer questions about the same substance as “medicine”

• Marijuana is unique in being the only substance with a wide spread, mostly socially acceptable recreational use as well as a potential medical indication.

• Solid science is needed to ground legal reform and public policy toward medical marijuana

Definition of Terms

• “Medical Marijuana” generally refers to the whole unprocessed marijuana plant or it’s crude extracts, which are not recognized as medicine by the US FDA

• Cannabinoids are a large family of chemicals related to delta-9- tetrahydrocannabinol (THC) • THC is marijuana’s main psychoactive ingredient

• Isolated and purified in 1965

• The amount of THC in MJ confiscated by police has been steadily increasing

• In 2012: THC concentrations in MJ averaged nearly 15% ( 3 % in the 1980’s) DAWN, 2011 http://www.samsa.gov/data/2k13/DAWN2k11ED

• > 100 other cannabinoids

• Occur in various ratios in the marijuana plant

NIDA, Drug Facts. “Is Marijuana a Medicine ? April 2014. www.drugabuse.gov

Definition of Terms

• Currently the 2 main cannabinoids of interest therapeutically

• THC: stimulates appetite and reduces nausea

• Already approved synthetic THC medications for these indications

• Cannabidiol (CBD): non-psychoactive, may be useful in reducing pain and inflammation, controlling epileptic seizures, and possibly even treating psychosis and addiction

NIDA, Drug Facts. “Is Marijuana a Medicine ? April 2014. www.drugabuse.gov

Pharmacology of Marijuana

• The cannabinoid receptor is a G-protein linked receptor, which inhibits adenylyl cyclase and stimulates potassium conductance. There are two known cannabinoid receptors: CB1 and CB2 • CB1 is found in the central nervous system including the basal

ganglia, substantia nigra, cerebellum, hippocampus, and cerebral cortex. It acts pre-synaptically and inhibits release of several neurotransmitters including acetylcholine, L-glutamate, gamma amino butyric acid (GABA), norepinephrine, dopamine, and 5-hydroxytryptamine

• CB2 is found peripherally in the immune system tissues (eg, splenic macrophages and B lymphocytes), peripheral nerve terminals, and vas deferens. It is postulated that it plays a role in regulation of immune responses and inflammatory reactions. Anandamide and palmitoylethanolamide are known endogenous cannabinoid receptor ligands.

Pharmacokinetics

• The pharmacokinetics and pharmacodynamics of delta-9 tetrahydrocannabinol (THC) vary by route of exposure as follows • Inhaled marijuana – After inhalation of marijuana smoke, onset

of psychoactive effects occurs rapidly with peak effects felt at 15 to 30 minutes and lasting up to four hours. These effects mirror plasma delta-9 tetrahydrocannabinol (THC) concentrations. Pulmonary bioavailability varies from 10 to 35 percent of an inhaled dose and is determined by the depth of inhalation along with the duration of puffing and breath holding

• Ingested marijuana – When compared to inhalation, cannabis ingestion has a delayed onset of psychoactive effects that ranges from 30 minutes to three hours. Clinical effects may last up to 12 hours. Orally administered cannabis has low bioavailability (5 to 20 percent) because of chemical degradation in gastric acid and substantial first-pass metabolism in the liver.

Some pharmacology facts:

• THC is highly lipid soluble accumulating in fatty tissues reaching a peak in 4-5 days

• Because of sequestration in fat, half-life is about 7 days. Complete elimination of a single dose may take up to 30 days

• Chronic users may take many weeks to clear their urine.

• THC metabolism occurs via hepatic cytochrome oxidases, CYP2C9 and 3A4. The primary active metabolite is 11-hydroxy THC

• THC crosses the placenta with fetal plasma concentrations 10 to 30 percent of maternal concentrations

• It also accumulates in breast milk at a concentration as high as eight times maternal plasma concentrations

Does the Scientific Literature Support the use of marijuana as medicine?

• Potential therapeutic impact:

• Glaucoma

• Chemotherapy induced nausea and vomiting

• AIDS-associated anorexia and wasting

• Chronic Pain ( neuropathic pain)

• Inflammation: animal studies in rheumatoid arthritis, ulcerative colitis, Chron’s Disease

• Multiple Sclerosis: Nabiximols (oral mucosal spray) appears to be effective for neuropathic pain, disturbed sleep, spasticity

• Epilepsy

Does the Scientific Literature Support the use of marijuana as medicine?

• Scientific study of cannabinoids has led to the development of 2 FDA approved oral medications and is leading the development of new pharmaceuticals that harness the benefits while minimizing the harmful side effects (including the “high”)

• Dronabinol (Marinol) contains THC. Treats nausea secondary to chemotherapy and wasting disease secondary to AIDS

• Nabilone (Cesamet) contains synthetic cannabinoid similar to THC for same indications

Does the Scientific Literature Support the use of marijuana as medicine?

• Sativex: oral mucosal spray

• Contains approximately equal parts THC and CBD

• Currently approved in UK and several European Countries

• Indication: spasticity caused by MS

• IN Phase III clinical trials in the US to establish effectiveness and safety in treating cancer pain

• Epidiolex: CBD based drug

• Has not yet undergone clinical trials

• Indication: certain forms of childhood epilepsy

• Prompted by anecdotal reports that high-CBD strain marijuana strain has been successful in treating a severe form of epilepsy called Dravet Syndrome

The Marijuana Plant Medical - Street - Recreational • Most marijuana sold in dispensaries as “medicine” is the same quality

and carries the same health risks as marijuana sold on the street

• The composition of herbal material, including THC content, varies widely depending on strain, cultivation, storage, and harvesting practices

• The methods of administration- smoked, vaproized, baked goods, teas, infused honey, elixirs, candies- do not ensure that a patient receives an identifiable, standardized, and hence reproducible dose

• All cannabis-based and cannabinoid medications should be subjected to the rigorous scrutiny of the FDA process • Standardized by identity, purity, potency, quality

• Accompanied by adequate directions for use in the approved medical indication

• Produced and distributed in a controlled fashion

• Risk/Benefit profiles have been defined in well-controlled clinical trials

** As long as it is illegal federally, marijuana is not available for research

• Method of delivery • Smoking raw cannabis remains the most common and easiest

route of delivery

• Quality Control • Dose will vary depending on the patient’s technique, functional

lung capacity, and aero-ingestion

• Contaminants • Aspergillus, heavy metals, organophosphate pesticides, tiny glass

beads, sand

• Monitoring for addiction • Frequent screening

• What are the risk mitigation strategies going to be ?

• How to separate “recreational from medical use?”

• Adverse Effects

Challenges of using medical marijuana

Greenwell. Journal of Pain and Palliative Care Pharmacotherapy. 2012;26:68-69. Leung. Journal of the American Board of Family Medicine. 2011;24(4):452.459.

Adverse Effects

• Short-Term • Marijuana intoxication causes well defined impairments in the

following brain functions: • Memory • sense of time • sensory perception • attention span • problem solving • verbal fluency • reaction time • psychomotor control

• The short-term effects of marijuana last approximately 1-4 hours, depending on potency of the marijuana, the route of administration, and the tolerance of the user.

• Marijuana intoxication impairs intellectual activities as well as activities that require bodily control, such as driving.

• Effects of long-term or heavy use • Addiction: in about 9% of users overall, 17% of those who begin

as adolescence and 25-50% of those who are daily users *

• Altered brain development *

• Poor educational outcome, with increased likelihood of dropping out of school *

• Cognitive impairment with lower IQ among those who are frequent users during adolescence*

• Diminished life satisfaction and achievement ( determined on the basis of subjective and objective measures as compared with such ratings in the general population)*

• Symptoms of chronic bronchitis

• Increased risk of chronic psychosis disorders( including schizophrenia) in persons with predisposition to such disorders

*The effect is strongly associated with initial marijuana use in early adolescence

Volkow,ND et al, Adverse Effects of Marijuana Use, NEJM 370(23); 2014:2219-2227.

Adverse Effects

Adverse Effects

• Lungs • Many of the same mutagens and carcinogens in nicotine are

found in marijuana smoke. Impact on lung function and respiratory cancer is in the process of being studied. • -4x more toxic than tobbacco.

• Immunologic • Evidence of immunosuppression due to impact on CB2 receptor

• Observed increase in mortality of HIV positive patients with cannabinoid abuse.

• Increased incidence of viral infections

• Cardiovascular • Compared with non-users, those who smoke weekly had a 2.5

fold greater likelihood of an MI, and those who smoked > 1 time per week had a 4.2 fold increased risk (Jouanjus,M et al, Cannibis Use:Signal of Increasing Risk of Serious Cardiovascular Disorders, J Am Heart Assoc. April 23,2014.)

Effects on Physical Health:

• Cannabis is the most prevalent drug, other than alcohol, found in oral fluid and blood of drivers

• According to a meta analysis, the overall risk of involvement in an accident increases 2 fold when a person drives soon after using marijuana

• The combination of marijuana and alcohol is worse than either substance alone with respect to driving impairment.

Cannabis and Driving Performance

Reisfield. Journal of Pain and Palliative Care Pharmacology. 2010;24:356-361 Hartman et al, Clin Chem 2013

• VHA policy does not administratively prohibit Veterans who participate in State marijuana programs from also participating in VHA substance abuse programs, pain control programs, or other clinical programs where the use of marijuana may be considered inconsistent with treatment goals.

• While patients participating in State marijuana programs must not be denied VHA services, the decisions to modify treatment plans in those situations need to be made by individual providers

Department of Veterans Affairs VHA DIRECTIVE 2011-004

Veterans Health Administration January 31, 2011

Washington, DC 20420

ACCESS TO CLINICAL PROGRAMS FOR VETERANS

PARTICIPATING IN STATE-APPROVED MARIJUANA PROGRAMS

(1) Prohibition on completing forms for participation in State marijuana programs.

(2) If a Veteran presents an authorization for marijuana to a VA provider or pharmacist, VA will not provide marijuana nor will it pay for it to be provided by a non-VA entity. NOTE: Possession of marijuana, even for authorized medical reasons, by Veterans while on VA property is in violation of VA regulation 1.218(a)(7) and places them at risk for prosecution under the Controlled Substances Act.

(3) If a patient reports participation in a State marijuana program to a member of the clinical staff, that information is entered into the “non-VA medication section” of the patient's electronic medical record following established medical facility procedures for recording non-VA medication use.

Department of Veterans Affairs VHA DIRECTIVE 2011-004

Veterans Health Administration January 31, 2011

Washington, DC 20420

ACCESS TO CLINICAL PROGRAMS FOR VETERANS

PARTICIPATING IN STATE-APPROVED MARIJUANA PROGRAMS

Case Studies

• Cannabis use and the prescription of opiate analgesics • Previously had the approach of don’t ask/don’t tell

• In the last ten years there has been an explosion of scrutiny regarding the prescription of opiate analgesics

• Marijuana is illegal for any use in the state of Pennsylvania and in the federal system. • I am personally unwilling to accept the medico-legal responsibility

for prescribing opiates to a patient using illegal, mind altering substances.

• My approach to ETOH is no different. • However ETOH is harder to detect.

• The conundrum of “medical” marijuana • California

Case Studies

• http://archinte.jamanetwork.com/article.aspx?articleid=1898878

• Medical Cannabis Laws and Opioid Analgesic Overdose Mortality in the United States, 1999-2010

• Medical cannabis laws are associated with significantly lower state-level opioid overdose mortality rates. Further investigation is required to determine how medical cannabis laws may interact with policies aimed at preventing opioid analgesic overdose.

Case Studies

• http://archinte.jamanetwork.com/article.aspx?articleid=1898878

• Does this mean that you might be softening your stance on THC and opioids? If not, this perhaps we should keep this article under wraps. ;)

Case I

• 60 yo patient with RA, lumbar and cervical pain/DDD

• NSAIDs, methotrexate, adalimumab

• On opiates since 2010.

• Originally 120 hydrocodone per month, 180 per month since 2013.

• 3 DAUs since October 2010. 2/3 positive for opiates, otherwise all negative.

• December 2014: positive for opiates and THC (confirmed)

Poll Question 1

• How do you approach this situation?

• Option A) Refuse to prescribe further opiates, initiate non-opiate therapy, refer to pain clinic.

• Option B) Discuss the concerns regarding combination of opiates and marijuana with the patient. Continue prescribing opiates as long as the THC eventually clears from the urine and does not recur.

Case I

• Pain consult: “Pt with hx of narcotic use for her chronic pain, recently found to have inappropriate DAUs and narcotics were stopped, cs for help with other pain management strategies”

• Started on gabapentin, ibuprofen, acetaminophen, IPRP consult

Case I

• DAU positive December 8th.

• Patient seen in pain clinic February 19

• DAU completely negative that day.

• Patient reports she tried marijuana from her son once to see if it would help.

• How to proceed now?

• Interestingly her pain is really no worse off the opiates.

Case II

• 60yo patient with diabetic neuropathy and chronic abdominal pain due to hepato/splenomagaly.

• Lesion on liver not felt to be HCCA-being monitored.

• Analgesic options are limited due to ESLD.

• Intolerant of gabapentin, TCAs.

• Tramadol no help.

• Patient maintained on oxycodone 5mg since 2011. First 60/month then 90/month and then 150 per month in May of 2014.

• Pain well controlled.

• Prescriptions on time.

• OAA signed November, 2011.

• DAUs

Case II

• 6/7/10- +THC, +opiate, no oxy screen. Not on opiates

• 7/10/12- +THC, -oxy screen, prior prescription 4/12/12

• 10/25/12- +THC, -oxy screen, prior prescription 7/10/12

• 1/24/13, all -, no oxy screen, prior prescription 12/14/12

• 1/13/14- +THC, +oxy screen

• 9/29/14- +THC, +oxy screen

• 1/8/15- +THC, + oxy screen

• PCP notes reviewed: Presence of THC is not mentioned.

• End of December 2014: new PCP

• Presence of THC noted: New PCP schedules an appointment requesting a repeat DAU and consent for long term treatment.

Poll Question # 2

• How do you proceed as the new PCP inheriting this patient?

• Option A) Continue prescribing opiates as the previous provider had done knowing that the THC was helping with analgesia and nausea.

• Option B) Taper the patient off opiates, institute non-opiate measures and refer to pain clinic.

• Option C) Taper the patient off opiates and discuss with the patient that therapy may resume when the urine clears and stays clear.

• Option D) Discuss with the patient that you will not prescribe opiates to a patient using THC, but will continue prescribing as long as the urine clears in a reasonable amount of time.

Case II

• Patient seen January 7th, 2015

• “she is ON A LOT OF OXYCODONE

• REFUSED TO HAVE EMG DONE

• POSITIVE FOR MARIJUANA

• EXPLAINED TO HER THAT SHE CAN NOT USE MARIJUANA

• IT IS ILLEGAL

• REPEAT URINE DRUG SCREEN AND IF SHE HAS IT AGAIN THEN OXYCODONE NEEDS TO BE STOP

• REFUSED PAIN CLINIC ”

• Long term consent signed.

• DAU repeated and was positive.

• Last prescription was 12/29/14

Case II

• 1/8/15

• Telephone contact report

• “positive marijuana again in her urine

• patient was informed that i will wean her off of the opioid and she will need to see the pain clinic

• patient aggreed ”

Case II

• 1/8/15

• Pain E-consult:

• “Impression: Diabetic neuropathy

• Plan: Concur with plan to wean oxycodone given ongoing marijuana use.

• Modalities such as tylenol and nsaids relatively contraindicated due to the patient's cirrhosis.

• Given that she is allergic to both gabapentin and nortryptiline, recommnend trial of pregabalin. Duloxetine could also be a future consideration.

• IPRP is not an option due to her marijuana use.”

Case II

• 2/5/15

• Palliative Care Consult

• “Previously, the Veteran was managed for chronic pain with oxycodone by her primary care provider. In review of her records during transition of care, it was noted that she has had prior DAUs positive for THC. Her opioid analgesic medication was thus discontinued. Consultation today for review.”

Case II

• 2/5/15

• Palliative Care Consult

• “I explained to the Veteran my understanding of VA opioid policy, that utilization of both substances was not consistent with guidelines and it would be recommended that she discontinue marijuana in order to continue to receive opioid analgesics from the VA. Veteran was agreeable to this recommendation. As veteran's life expectancy is likely greater than six months, formal pain management recs would be governed by the pain clinic. Consultation to this clinic was placed for additional review. Veteran satisfied with recs, and plans to schedule follow up appointment with pain clinic for additional review. A prescription for 2 weeks of oxycodone was written.”

Case II

• 2/26/15

• Pain Consult

• Very reluctant to consider other neuromodulators due to her concern over cognitive side effects.

• “Patient is somewhat vague about her marijuana use. She indicates that she mostly drank it in tea and rarely smoked it and was only using it for it's medical properties of analgesia and treatment of nausea and vomiting. She states that it has been six weeks since she last used any, but in viewing the interaction between her and her sister it is not clear just how reliable and accurate any of this is. She claims not to have smoked anything in six weeks and when I stated that based on the pattern of use and the time elapsed she should be negative today she is hopeful but not confident.”

Case II

• 2/26/15

• Pain Consult

• “I spoke with the patient and her sister at great length. Regarding treatment options for this condition and the concomitant use of marijuana and opiates. This is a controversial area on which not all providers agree and is especially controversial in Pennsylvania/VAHCS for which marijuana is illegal for all uses. Personally I have no tolerance with the chronic use of any euphoria causing substance of abuse in conjunction with opiate treatment be it legal (ETOH) or illegal. I have extra concerns from a medico-legal liability standpoint in continuing to prescribe opiates to any patient with ongoing documented use of an illegal substance and my tolerance for such is zero. This view shared by the majority of providers but not all, as evidenced by some providers who will continue to prescribe opiates to chronic marijuana users.”

Case II

• 2/26/15

• Pain Consult

• “The options in this case are limited by the patient's co-morbidities and the nature of her pain. They are also limited by the patient's pre-concieved conviction that other therapies (pregabalin, duloxetine, etc.) will cause cognitive side effects. I pointed out the incongruity of this notion in the context of her use of marijuana. In any case, these therapies are likely destined to fail for this reason.

• In any case, I recommend the resumption of her opiate therapy with the condition that she cease marijuana use and remain free from it's use. I make this recommendation due to the limited options otherwise and the fact that her pain was controlled and she was functional and because she seems to have good social support. She will need to be monitored closely with frequent DAUs and will need to sign the new consent for long term treatment, presuming that her PCP agrees.”

Case II

• 2/26/15

• Pain Consult

• DAU was completely negative

What to say to your patients • Federally illegal so we can’t prescribe

• Facilities need to develop a unified approach

• Discuss in a dispassionate and non-judgmental and supportive manner …the evidence • Patients should be warned that the adverse effects of reported in

long term use are unclear

• Could also advise on the adverse effects reported in long-term recreational use such as the development of dependence/addiction, cognitive impairment, dangers of driving impaired

• Addressing positive marijuana in drug screens • Counseling, review informed consent, warning that continued use

will result in tapering opioid, offer addiction services if the patient needs help

• If the patient reports that it is “ medical marijuana” • Refer to the VHA Directive : … the decisions to modify treatment

plans in those situations need to be made by individual providers

References

• “Understanding the effects of Marijuana Use” Handout for patients from VHA Center of Excellence in Substance Abuse Treatment and Education

• Geppert, Cynthia, Legal and Clinical Evolution of Veterans Health Administration Policy on Medical Marijuana, Federal Practitioner, March 20, 2014

• NIDA Drug Facts. “Is Marijuana Medicine?” April 2015. www.drugabuse.gov

• Volkow,ND et al, Adverse Effects of Marijuana Use, NEJM 370;23 June 5,2014

Reference Slides

Clinical Conditions with Symptoms That May Be Relieved by Treatment with Marijuana or Other Cannabinoids

Volkow,ND et al, Adverse Effects of Marijuana Use, NEJM 370(23); 2014:2219-2227.

Glaucoma Early evidence of the benefits of marijuana in patients with glaucoma (a disease associated with increased pressure in the eye) may be consistent with its ability to effect a transient decrease in intraocular pressure(53,54) but other, standard treatments are currently more effective. THC, cannabinol, and nabilone (a synthetic cannabinoid similar to THC), but not cannabidiol, were shown to lower intraocular pressure in rabbits(55,56) More research is needed to establish whether molecules that modulate the endocannabinoid system may not only reduce intraocular pressure but also provide a neuroprotective benefit in patients with glaucoma(57) Nausea Treatment of the nausea and vomiting associated with chemotherapy was one of the first medical uses of THC and other cannabinoids(58) THC is an effective antiemetic agent in patients undergoing chemotherapy,(59) but patients often state that marijuana is more effective in suppressing nausea. Other, unidentified compounds in marijuana may enhance the effect of THC (as appears to be the case with THC and cannabidiol, which operate through different antiemetic mechanisms).(60) Paradoxically, increased vomiting (hyperemesis) has been reported with repeated marijuana use.

AIDS-associated anorexia and wasting syndrome Reports have indicated that smoked or ingested cannabis improves appetite and leads to weight gain and improved mood and quality of life among patients with AIDS(61) However, there is no long-term or rigorous evidence of a sustained effect of cannabis on AIDS-related morbidity and mortality, with an acceptable safety profile, that would justify its incorporation into current clinical practice for patients who are receiving effective antiretroviral therapy(62). Data from the few studies that have explored the potential therapeutic value of cannabinoids for this patient population are inconclusive (62). Chronic pain Marijuana has been used to relieve pain for centuries. Studies have shown that cannabinoids acting through central CB1 receptors, and possibly peripheral CB1 and CB2 receptors,63 play important roles in modeling nociceptive responses in various models of pain. These findings are consistent with reports that marijuana may be effective in ameliorating neuropathic pain (64,65) even at very low levels of THC (1.29%) (66) Both marijuana and dronabinol, a pharmaceutical formulation of THC, decrease pain, but dronabinol may lead to longer-lasting reductions in pain sensitivity and lower ratings of rewarding effects (67).

Inflammation Cannabinoids (e.g., THC and cannabidiol) have substantial antiinflammatory effect sbecause of their ability to induce apoptosis, inhibit cell proliferation, and suppress cytokine production(68). Cannabidiol has attracted particular interest as an antiinflammatory agent because of its lack of psychoactive effects.58 Animal models have shown that cannabidiol is a promising candidate for the treatment of rheumatoid arthritis (58) and for inflammatory diseases of the gastrointestinal tract (e.g., ulcerative colitis and Crohn’s disease) (69) Multiple sclerosis Nabiximols (Sativex, GW Pharmaceuticals), an oromucosal spray that delivers a mix of THC and cannabidiol, appears to be an effective treatment for neuropathic pain, disturbed sleep, and spasticity in patients with multiple sclerosis. Sativex is available in the United Kingdom, Canada, and several other countries(70,71) and is currently being reviewed in phase 3 trials in the United States in order to gain approval from the Food and Drug Administration. Epilepsy In a recent small survey of parents who use marijuana with a high cannabidiol content to treat epileptic seizures in their children,(72) 11% (2 families out of the 19 that met the inclusion criteria) reported complete freedom from seizures, 42% (8 families) reported a reduction of more than 80% in seizure frequency, and 32% (6 families) reported a reduction of 25 to 60% in seizure frequency. Although such reports are promising, insufficient safety and efficacy data are available on the use of cannabis botanicals for the treatment of epilepsy (73). However, there is increasing evidence of the role of cannabidiol as an antiepileptic agent in animal models (74).

Passive Marijuana Inhalation and Drug Screens

• 1988: Mule’ et al. conducted a study involving eight marijuana smokers (each smoking four cigarettes with 27 mg THC per cigarette) and three nonsmokers passively inhaling the marijuana smoke in a closed 10x10x8 ft. room with no windows. He consistently reported less than 10 ng/ml of THC metabolites as a result of passive inhalation.

• 1985 - 1990: Cone et al performed a series of rigorous double-blind

marijuana passive inhalation studies. The maximum urine concentration of the THC-acid metabolite obtained by GC/MS analysis was 12 ng/ml. The conditions during this test were so extreme, that all the subjects wore goggles to protect their eyes from the dense smoke in the room.

• The current cut off for cannabinoids on all Urine Drug Screens is 50 ng/ml