Office Of Medical Cannabis Dosages And Compositions Report .
A Review of Medical Cannabis Studiesrelating to Chemical Compositions andDosages for Qualifying Medical ConditionsMAY 2018
A REVIEW OF MEDICAL CANNABIS STUDIES RELATING TO CHEMICALCOMPOSITIONS AND DOSAGES FOR QUALIFYING MEDICAL CONDITIONSA Review of Medical Cannabis Studies relating to Chemical Compositions and Dosagesfor Qualifying Medical ConditionsMinnesota Department of HealthOffice of Medical CannabisPO Box 64882St. Paul, MN ww.health.state.mn.usAs requested by Minnesota Statute 3.197: This report cost approximately 7,000 to prepare, including staff time,printing and mailing expenses.Upon request, this material will be made available in an alternative format such as large print, Braille or audiorecording. Printed on recycled paper.2
A REVIEW OF MEDICAL CANNABIS STUDIES RELATING TO CHEMICALCOMPOSITIONS AND DOSAGES FOR QUALIFYING MEDICAL CONDITIONSContentsExecutive Summary . 4Introduction . 11Cancer . 12Severe or Chronic Pain. 12Nausea or Severe Vomiting . 18Cachexia or Severe Wasting . 21Glaucoma . 24Human Immunodeficiency Virus or Acquired Immune Deficiency Syndrome . 27Tourette Syndrome. 32Amyotrophic Lateral Sclerosis . 35Seizures, including those characteristic of epilepsy . 36Severe and persistent muscle spasms, including those characteristic of multiple sclerosis 42Multiple Sclerosis. 42Spinal Cord Injury. 45Inflammatory Bowel Disease . 58Terminal illness . 62Intractable Pain. 62Post-Traumatic Stress Disorder . 77Autism Spectrum Disorder . 78Obstructive Sleep Apnea . 803
A REVIEW OF MEDICAL CANNABIS STUDIES RELATING TO CHEMICALCOMPOSITIONS AND DOSAGES FOR QUALIFYING MEDICAL CONDITIONSExecutive SummaryOn May 29, 2014 the Governor of Minnesota signed the medical cannabis therapeutic use law:2014 Minnesota Laws chapter 311. This Act is designed to enable truly sick patients to engagein the therapeutic use of cannabis while preventing it from being misused or diverted from itsmedical purpose.This report summarizes clinical trials and prospective observational studies in humans,published in peer reviewed journals, which focus on medical cannabis formulations consistentwith Minnesota’s medical cannabis program. It is produced in fulfillment of Minnesota StatutesSection 152.25, subdivision 2. The report was first produced in December, 2014, and it isupdated annually.4
A REVIEW OF MEDICAL CANNABIS STUDIES RELATING TO CHEMICALCOMPOSITIONS AND DOSAGES FOR QUALIFYING MEDICAL CONDITIONSMedical conditions included in each update of this report are a combination of qualifyingconditions named in the statute establishing the program and qualifying conditions that havebeen added since then. The medical conditions identified in the statute for inclusion inMinnesota’s medical cannabis program are:123456789Cancer, if the underlying condition or treatment produces one or more of the following:a. Severe or chronic pain;b. Nausea or severe vomiting; orc. Cachexia or severe wastingGlaucomaHuman immunodeficiency virus or acquired immune deficiency syndromeTourette’s syndromeAmyotrophic lateral sclerosisSeizures, including those characteristic of epilepsySevere and persistent muscle spasms, including those characteristic of multiple sclerosisCrohn’s disease (expanded to Inflammatory Bowel Disease in 2016)Terminal illness, with a probable life expectancy of under one year, if the illness or itstreatment produces one or more of the following:a. Severe or chronic pain;b. Nausea or severe vomiting; orc. Cachexia or severe wastingOn December 2, 2015 the Commissioner announced his decision to add intractable pain to the listof the program’s qualifying medical conditions, effective August 1, 2016. Similarly, post-traumaticstress disorder (PTSD) was added, effective August 1, 2017, and autism spectrum disorder andobstructive sleep apnea were added, effective August 1, 2018.There are relatively few clinical trials, especially large clinical trials that can produce the mostdefinitive results. In recent years the number of trials has increased to some degree, perhapsreflecting the commercialization of medical cannabis products around the world over the pastfew decades. Following are summary observations for each section.5
Cancer: painCancer: cachexia/wastingTrial results suggest a combination of THCand CBD might be more effective than THCalone and that doses of THC higher thanapproximately 25 mg, even when dividedover the course of a day, might be poorlytolerated by a substantial number of patients.The recently completed international trials ofapproximately 1:1 THC:CBD oromucosal spray(nabiximols, brand name Sativex) failed tomeet their primary endpoints. However, apre-specified pooled analysis of patients fromU. S. Centers, from 2 of the 3 trials, showedbetter pain control with Sativex than withplacebo. The maximum daily dosage allowedwas 10 sprays per day, providing 27 mg THCand 25 mg CBD per day. However, patients inthe Sativex arms of these trials self-titrated toan average of 6.3 or 6.4 sprays per day,providing approximately 17 mg THC and 16mg CBD per day.Some small early trials showedeffectiveness with doses of plant-derivedTHC 10 to 15 mg three to four times dailyon days of chemotherapy infusion. Latertrials with dronabinol, mostly in cancerpatients not receiving chemotherapy, areless encouraging. Using doses of 5.0 to7.5 mg daily in divided doses there waseither modest effectiveness compared toplacebo or inferior effectivenesscompared to a standard appetiteenhancing drug, and a substantialnumber of patients could not toleratethese doses. A large trial with cannabisextract treatment arms of relativelysmall doses of THC only (2.5 mg twicedaily) or THC CBD (2.5 mg THC/1.0 mgCBD twice daily) was stopped early forlack of effectiveness, yet dose reductionswere necessary in a third of both groups.Cancer: nausea and vomitingSeveral studies of plant-derived THC forchemotherapy-induced nausea andvomiting (CINV) from the late 1970s used 10to 18 mg THC starting an hour or two beforechemotherapy initiation, then repeating thedose every 2 to 4 hours for an additional 2to 4 doses over 12 to 24 hours. Clinical trialsof dronabinol, synthetic delta-9-THC, haveused daily doses similar to the trials ofplant-derived THC from the 1970s: 30 to 80mg/day in divided doses. Not everyone cantolerate these doses, and the FDArecommends a lower dronabinol dose forCINV, stating most patients respond to 5 mgthree or four times daily.GlaucomaCBD does not appear to be effective atlowering intraocular pressure (IOP) andmight even increase it. There is someevidence that even relatively low (5 mg)single doses of THC significantly reduces IOPfor 4 to 5 hours before it returns to baseline,but this isn’t a consistent finding acrossstudies. Larger single doses (20 and 25 mg)appear to reduce IOP longer (10 hours), butwith a high occurrence of intolerable sideeffects.HIV/AIDSEach of the studies identified useddronabinol and assessed effect on appetiteand weight. Most used 5.0 to 7.5 mg daily in
A REIVEW OF MEDICAL CANNABIS STUDIES RELATING TO CHEMICALCOMPOSITIONS AND DOSAGES FOR QUALIFYING MEDICAL CONDITIONS2 or 3 divided doses, consistent with FDAlabel recommendations. Though mostpatients tolerated this dose well, asubstantial minority could only tolerate 2.5mg daily. Results from three trials thatenrolled current marijuana users suggestcurrent marijuana users can tolerate higherdoses, in the range of 20 to 40 mg daily individed doses.SeizuresTourette syndromeResults of some of these trials and a safetystudy show the importance of monitoringliver enzymes when a patient is using CBD –especially when valproate is used at the sametime. In addition, there is growing evidenceof interaction between CBD and standardanti-epileptic drugs – especially clobazam.Two small studies of oral, plant-derived THC(source not specified) in adult TS patientsused single daily doses of 2.5 mg to 10 mg.About a third of the patients needed todecrease dose because of unacceptable sideeffects. Together, these studies providemodest evidence of effectiveness at reducingtic severity.Three additional clinical trials are beingorganized. One will use nabiximols spray(approximately equal amounts of THC andCBD), one will use dronabinol (synthetic THC)and palmitoylethanolamide, and one will usevaporized cannabis flower with differentTHC:CBD ratios.Amyotrophic Lateral SclerosisThe two small trials in ALS patients that wereidentified used dronabinol. One was reportedin an abstract with few details, but startedpatients on 2.5 mg daily and titrated up to amaximum daily dose of 10 mg. The secondused 10 mg daily in two divided doses. Bothstudies indicated patients tolerated thedronabinol doses well, but with little clearevidence of effectiveness. A third trial withno published results yet used nabiximolsspray (approximately equal amounts of THCand CBD).7Recent studies mostly focusing on childrenhave used 99% CBD extract in olive oil oralsolution as an adjunct to current antiepileptic drug therapy, starting at a dose of 2to 5 mg/kg/day, titrating up over 2 to 4weeks to a goal of 10, 20, 25, or 50mg/kg/day (most frequently used 20mg/kg/day).Muscle spasmsResults of numerous trials focusing onspasticity and muscle spasm have beenpublished, mostly with multiple sclerosispatients, but also some with spinal cordinjury patients. Whether in combination withCBD in various ratios or as a single agent(dronabinol), THC has been used in averagedosages of 20 to 25 mg/day in divided doses.Dosages are usually started fairly low andthen titrated up to achieve a balancebetween symptom reduction and appearanceof side effects. From the trial experience, itappears that doing this titration over weeks,rather than over days, helps to reduceincidence and severity of side effects. Thereis some indication that THC is more effectivein reducing spasticity and spasm at higherdoses and that higher doses are bettertolerated when given in conjunction withCBD in a THC:CBD ratio of 1:1 (versus 2:1 or3:1). But some patients cannot tolerate evenquite low doses of THC. Treatment appearsto be effective in only a subset of patients,
A REIVEW OF MEDICAL CANNABIS STUDIES RELATING TO CHEMICALCOMPOSITIONS AND DOSAGES FOR QUALIFYING MEDICAL CONDITIONSperhaps around half, and whether or nottreatment will be effective can generally bedetermined within a few weeks.Inflammatory bowel diseaseAt this point there is little guidance fromclinical trials on composition or dosing,though there is an evident interest inproducts that are at least relatively high inCBD. The three clinical trials published todate are small. One used 99.5% pure CBDpurified from cannabis extraction at a doseof 5 mg sublingually twice a day (Naftali2017). The second used smoked cannabiswith a THC CBD ratio of approximately50:1 (Naftali 2013). The third used a “CBDrich cannabis extract” (Irving 2018). Thetrial now in the planning stage will use CBDcapsules.Terminal illnessRelevant studies can be found in othersections of this report, particularly the cancersections. No published medical cannabistrials were found that specifically targetedpatients with short life expectancy, cuttingacross medical conditions.Intractable painFor the Minnesota medical cannabis programintractable pain is defined as pain whosecause cannot be removed and, according togenerally accepted medical practice, the fullrange of pain management modalitiesappropriate for the patient has been usedwithout adequate result or with intolerableside effects. Trials of cannabis for pain in theliterature generally follow this definition inthat their inclusion criteria specify patients8with pain inadequately controlled withstandard pain medications. The trialsuniformly had the participants continuetaking their routine pain medications, so theyassess the value of cannabis treatment as anadjunct to other pain medications.The quality of most of the studiessummarized in this section is formallyassessed in a report by the MN Evidencebased Practice Center called, “MedicalCannabis for Non-Cancer Pain: A df)Six of the studies assessed in that report arenot summarized here because they used thesynthetic cannabinoid nabilone, which issimilar to – but distinct from – THC.Most of the 16 trials summarized here arerelatively small (seven have 100participants) and short (only 3 of thecontrolled trials are longer than 5 weeks) andthey are spread across multiple types of pain.These are important limitations to their valuein giving understanding of the potential forcannabis products in pain management.Eleven of the 16 trials studied anapproximately 1:1 ratio of THC: CBD oromucosal spray (in most cases nabiximols,brand name Sativex) vs. placebo. Averagedose in the clinical trials, after the titrationperiod, of the 1:1 THC: CBD spray werearound 6 to 10 sprays per day, representing adaily dose of approximately 15 to 27 mg THCand CBD per day.Two of the articles report studies of longterm use of nabiximols. Results showed noevidence of tolerance developing withdosages a bit lower than during theunderlying clinical trials lasting a month ortwo.
A REIVEW OF MEDICAL CANNABIS STUDIES RELATING TO CHEMICALCOMPOSITIONS AND DOSAGES FOR QUALIFYING MEDICAL CONDITIONSThree trials studied oral dronabinol, syntheticTHC, vs. placebo. Two of them reporteddosage after titration, ranging from 5 to 12.7mg/day.Post-traumatic stressdisorderNo randomized, controlled clinical trials havebeen completed for cannabis producttherapy in PTSD patients. Two such trials arenow recruiting patients; their expectedcompletion dates are 2019 and 2020. In one,three types of smoked cannabis (more THCthan CBD; more CBD than THC; and equalamounts of THC and CBD) are compared witheach other and to placebo in alleviatingsymptoms and in occurrence of adverse eventsamong 76 U.S. veterans with treatmentresistant PTSD. Participants may smoke up to1.8 grams cannabis per day. The second trialcompares three types of vaporized driedcannabis (high THC/low CBD; high THC/highCBD; low THC/low CBD) with each other andwith placebo in alleviating symptoms and inoccurrence of adverse events among 42patients with treatment-resistant PTSD.Participants are allowed to vaporize up to 2grams of plant material per day as needed.A small short-term, open-label (no controlgroup) study assessed the safety and benefitof THC administered under the tongue. Tenpatients with PTSD received 5 mg THCdissolved in olive oil twice daily for threeweeks. Statistically significant improvementbetween baseline and end of study was seenfor PTSD hyperarousal component score,Clinical Global Impression-Severity scale,Clinical Global Impression – Improvementscale, sleep quality, nightmare frequency,and nightmare effects. Mild side effects werereported by four participants, with nonedropping out due to side effects.9Autism Spectrum DisorderNo randomized, controlled clinical trials havebeen completed for cannabis or cannabinoidsas therapy for ASD. However, two have beenregistered on www.clinicaltrials.gov and arenow under way. In addition, an abstractpresented as a poster at the AmericanAcademy of Neurology Annual Meeting inApril, 2018 was recently published. One ofthe planned trials and the retrospective casereview presented at the AAN use a high CBDoral product (20:1 CBD:THC). In both, themaximal allowed dose of CBD is 10mg/kg/day. The second planned trial usescannabidivarin (CBDV).Obstructive Sleep ApneaObstructive sleep apnea (OSA) is a sleepdisorder characterized by repetitive episodesof complete (apnea) or partial (hypopnea)collapse of the upper airway (mainly theoropharyngeal tract) during sleep, with aconsequent cessation/reduction of airflow.The obstructive events cause a progressiveasphyxia that increasingly stimulatesbreathing efforts against the collapsedairway, typically until the person isawakened. These episodes cause acutephysiological disruptions includingfragmented sleep, intermittent hypoxia, andexaggerated fluctuations in heart rhythm,blood pressure, and intrathoracic pressure.Over time, the acute disruptions lead tochronic conditions such as hypertension andheart disease, reduced cognitive function,depression, and impaired performance atwork and while driving, as well as prematuredeath.
A REIVEW OF MEDICAL CANNABIS STUDIES RELATING TO CHEMICALCOMPOSITIONS AND DOSAGES FOR QUALIFYING MEDICAL CONDITIONSOne randomized, placebo-controlled clinicaltrial of cannabis or a cannabinoid product hasbeen published (Carley 2018). This six weektrial of dronabinol (synthetic THC) at doses of2.5 mg and 10 mg daily, taken at bedtime,found a modest treatment benefit fromdronabinol with substantial variation amongpatients in degree of response. The authors’responder analysis suggests only a portion –likely a rather small portion – of OSA patientsreceive a clinically meaningful reduction inAHI from the therapy used in this trial.10
A REIVEW OF MEDICAL CANNABIS STUDIES RELATING TO CHEMICALCOMPOSITIONS AND DOSAGES FOR QUALIFYING MEDICAL CONDITIONSIntroductionOn May 29, 2014 the Governor of Minnesotasigned the medical cannabis therapeutic uselaw: 2014 Minnesota Laws chapter 311. ThisAct is designed to enable truly sick patientsto engage in the therapeutic use of cannabiswhile preventing it from being misused ordiverted from its medical purpose.This report summarizes clinical trials andprospective observational studies in humans,published in peer-reviewed journals, thatfocus on medical cannabis formulationsconsistent with Minnesota’s medicalcannabis program. It was produced infulfillment of Minnesota Statutes Section152.25, Subdivision 2. The report is updatedannually.Medical conditions included in each updateof this report are a combination of qualifyingconditions named in the statute establishingthe program and qualifying conditions thathave been added since then. The medicalconditions identified in the statute forinclusion in Minnesota’s medical cannabisprogram are:1234511Cancer, if the underlying conditionor treatment produces one or moreof the following:a. Severe or chronic pain;b. Nausea or severe vomiting; orc. Cachexia or severe wastingGlaucomaHuman immunodeficiency virus oracquired immune deficiencysyndromeTourette’s syndromeAmyotrophic lateral sclerosis6789Seizures, including thosecharacteristic of epilepsySevere and persistent musclespasms, including thosecharacteristic of multiple sclerosisCrohn’s disease (expanded toInflammatory Bowel Disease in2016)Terminal illness, with a probablelife expectancy of under oneyear, if the illness or itstreatment produces one ormore of the following:d. Severe or chronic pain;e. Nausea or severe vomiting; orf. Cachexia or severe wastingOn December 2, 2015 the Commissionerannounced his decision to add intractablepain to the list of the program’s qualifyingmedical conditions, effective August 1, 2016.Similarly, post-traumatic stress disorder(PTSD) was added, effective August 1, 2017,and autism spectrum disorder andobstructive sleep apnea were added,effective August 1, 2018.To accomplish this review, the NationalLibrary of Medicine’s MEDLINE database wassearched using key words appropriate foreach qualifying medical condition in theMinnesota medical cannabis programstatute. Articles that appeared to be resultsof clinical trials or reviews of clinical trialswere accessed through the MDH library forexamination. References in such articles werestudied to identify additional articles thatwere not found on the initial search. Thiscontinued in an iterative fashion until noadditional relevant articles were found.
A REIVEW OF MEDICAL CANNABIS STUDIES RELATING TO CHEMICALCOMPOSITIONS AND DOSAGES FOR QUALIFYING MEDICAL CONDITIONSFinally, the government maintained web siteof registered clinical trials, clinicaltrials.gov,was searched to learn about trials currentlyunder way or under development and tocheck whether additional articles oncompleted trials could be found.The body of this report contains a section foreach of the 13 qualifying medical conditions.At the beginning of each section (orsubsection, in the case of cancer) there arecomments providing an overview of thescientific articles that follow. Below thecitation for each article is a condenseddescription of the study and its results.Trials involving non-smokeable medicalcannabis usually use either extractions ofcannabis, sometimes with processing thatenriches specific components of the plant’sconstituent parts, or synthetic cannabinoids.Cannabinoids are a class of oxygencontaining aromatic hydrocarbons founddistinctively in plants from the genusCannabis.The two cannabinoids typically found ingreatest quantity in cannabis plants aredelta-9-tetrahydrocannibinol (typicallyreferred to as THC) and cannabidiol (CBD).THC is the cannabinoid usually present ingreatest quantity and it is psychoactive,acting as a prominent cause of the euphoria- and sometimes dysphoria, - perceptions oftime distortion, and so forth that are wellknown from recreational use of marijuana.Both THC and CBD have been studiedextensively in pre-clinical research, both inbasic laboratory studies and in animalmodels. Both have attributes and effects inanimal models that suggest beneficialeffects with medical use in humans. CBD isnot psychoactive and might attenuate thepsychoactive effects of THC in somepatients. There are relatively few clinical12trials, especially large clinical trials that canproduce the most definitive results. Inrecent years the number of such trials hasincreased to some degree, perhapsreflecting the commercialization of medicalcannabis products around the world overthe past few decades.CancerIf the underlying condition or treatmentproduces one or more of the following:severe or chronic pain, nausea or severevomiting, or cachexia or severe wasting(three separate sections presented below)Severe or Chronic PainTwo early trials studied delta-9-THC sourcedfrom the U.S. government (Noyes J ClinPharmacol 1975; Noyes Clin Pharmacol Ther1975) and gave single oral administrations of5, 10, 15, and 20 mg THC to adult cancerpatients. Oral administration of 20 mg wasnot well- tolerated. Studies where similardaily doses of THC, or larger, divided intosmaller dose administrations over the courseof the day, would be helpful. But such studieswere not found in the published literatureand do not appear to be in the planningphases on clinicaltrials.gov.Later, larger trials have studied nabiximols,the US Adopted Name for Sativex.Nabiximols is an oromucosal spray producedthrough extraction and processing of a strainof Cannabis sativa that results in high andstable concentrations of delta-9-THC andCBD and minor amounts of other
A REIVEW OF MEDICAL CANNABIS STUDIES RELATING TO CHEMICALCOMPOSITIONS AND DOSAGES FOR QUALIFYING MEDICAL CONDITIONScannabinoids and terpenes. Each 100 microliter actualization (spray) contains 2.7 mgTHC and 2.5 mg CBD. The high dose group inPortenoy 2012, at least 11 sprays per day (3in the AM, 8 in the PM), was not welltolerated. 11 sprays delivers 29.7 mg THC(8.7 mg in the AM, 21.6 mg in the PM) and 25mg CBD. Patients in Johnson 2010 selftitrated to an average of 8.75 sprays (23.6 mgTHC, 21.9 mg CBD), delivered over the courseof a day. Patients taking nabiximols in theJohnson 2010 study tolerated it fairly well.The Johnson 2010 study also had a grouptaking a cannabis extract that had only THC.Patients in this group self-titrated to 8.34sprays over the course of a day (22.5 mgTHC), tolerating it fairly well, with a sideeffect profile similar to the THC/CBD group.Patients in the Lynch 2014 study self-titratedto a mean of 8 sprays (21.6 mg THC and 20.0mg CBD) spread throughout the day, with nostudy withdrawals due to treatment sideeffects. In the large study reported inLichtman 2017 patients self-titrated to 6.4sprays per day (17.3 mg THC and 16.0 mgCBD). Results in Fallon 2017 were verysimilar. These studies, as a group, suggest thewisdom of dividing a day’s total dose of abalanced THC/CBD product, with total THCand CBD in the range of 15 to 25 mg (each)per day over multiple differentadministrations to mitigate side effects. TheJohnson 2012 extension study lacked largenumbers of patients followed long-term onnabiximols, but nevertheless it does providesome evidence of effectiveness over manymonths with no evidence of need for doseescalation over time.13Fallon MT, Lux EA, McQuade R, Rossetti S,Sanchez R, et al. Sativex oromucosal sprayas adjunctive therapy in advanced cancerpatients with chronic pain unalleviated byoptimized opioid therapy: two double-blind,randomized, placeo-controlled phase 3studies. Br J Pain 2017;11:119-133.This paper describes two clinical trials. Trial#1 methodology, number and location ofstudy centers, and number of patientsrandomized to Sativex and placebo are verysimilar, but not quite the same, as the studydescribed in Lichtman 2017. Drug exposurealso very similar. Primary outcome was thebiggest difference, with Sativex groupshowing 7.2% improvement from baseline inpain NRS score and the placebo groupshowing a 9.5% reduction (differencebetween groups not statistically significant).Trial #2 required 15% reduction in NRS painscore at end of two week titration in order tomove on to the three week treatment period.The average number of sprays during thetwo-week titration period was 6.4 (i.e. verysimilar to what is reported in Trial #1 [6.3sprays/day in Sativex arm] and in Lichtman2017 [6.4 sprays/day]). This paper alsodescribes how, in pre-specified subanalysesof US participants in Trial #1 and in Lichtman2017 had a primary efficacy outcome thatfavored Sativex – especially for participants 65.
A REIVEW OF MEDICAL CANNABIS STUDIES RELATING TO CHEMICALCOMPOSITIONS AND DOSAGES FOR QUALIFYING MEDICAL CONDITIONSJohnson JR, Burnell-Nugent M, LossignolD, Ganac-Motan ED, et al. Multicenter,double-blind, randomized, placebocontrolled, parallel-group study of theefficacy, safety, and tolerability of THC:CBD extract and THC extract in patientswith intractable cancer-related pain. JPain Symptom Manage 2010; 39:167179.The effect of two weeks of treatment withnabiximols, THC extract, or placebo wasstudied in this double-blind, randomized,placebo-controlled, parallel group studyinvolving 177 adult cancer patients from 28European centers. The patients wererequired to have advanced cancer with painnot adequately controlled despite optimizedopioid management. Patients withchemotherapy within the preceding twoweeks were excluded. Patients wererandomized to nabiximols, to a cannabisextract containing only THC (2.7 mg per 100micro-liter spray), or placebo spray.Patients self-titrated with the instruction ofincreasing the number of sprays each day bya maximum of 50% until they either hadsatisfactory relief of their symptoms ordeveloped unwanted side effects. Sprayswere to be spread throughout the day, withat least 15 minutes between sprays.Maximum number of sprays allowedwithin a 3 hour period was 8 andmaximum within a 24 hour period was 48.The mean number of sprays in thenabiximols group was 8.75 (23.6 mg THC,21.9 mg CBD) and the average number ofsprays in the THC group was 8.34 (22.5 mgTHC). The co- primary end-point wasreduction in pain score between baselineand end of study. 43% of patients in theTHC/CBD group achieved a 30% or greaterreduction in their pain score, twice the14number of patients who achieved thisresponse in the THC and placebo groups.A higher percentage of patientsexperienced somnolence (13%), dizziness(12%), and confusion (7%) in thenabiximols group than in placebo.Incidence of these side effects was similarin the THC/CBD and THC groups.However, 3 episodes of hypotension wereseen in the nabiximols group and nonewas observed in the THC or placebogroups. Side effects leading to studywithdrawal occurred in 1
COMPOSITIONS AND DOSAGES FOR QUALIFYING MEDICAL CONDITIONS . 2 . A Review of Medical Cannabis Studies relating to Chemical Compositions and Dosages for Qualifying Medical Conditions . Minnesota Department of Health Office of Medical Cannabis PO Box 64882 St. Paul, MN 55164-0882 651-201-5598 . health.can
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and "medical cannabis, medical cannabis product, or cannabis product" as defined by subdivision (af) of section 19300.5 of the Business and Professions Code. "Cannabis product symbol " means the image established by the Department to indicate that a manufactured product contains THC. "CBD" means the compound cannabidiol.
The medical use of preparations derived from the Cannabis sativa plant has a long history. However, by the twentieth century, medical use of cannabis had largely declined, and its consumption for medical purposes was already very limited when in 1961 cannabis was included in the United Nations Single Convention on Narcotic Drugs and classified as
5 Cannabis Regulation in Europe: Country Report Denmark transnationalinstitute how the closure of, and subsequent increased police attention to cannabis sale in, Pusher Street has led to the dispersal of the cannabis market, with more covert cannabis sale occurring in hash clubs throughout Copenhagen (
cannabis activity and an M-license to engage in medicinal commercial cannabis activity. The exception is testing laboratories, which may test cannabis goods for both license types. Ownership An owner is a person who: holds at least 20 percent aggregate ownership interest in a commercial cannabis business; is a chief executive offcer or
Cannabis products must be in packaged in a child-resistant container and be labelled with the standardized cannabis symbol, the mandatory health warning message, and include specific product information (e.g., brand name of the cannabis product, class of cannabis, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) information, licence
Academic writing is cautious, because many things are uncertain. When we put forward an argument, point of view or claim, we know that it can probably be contested and that not everybody would necessarily agree with it. We use words and phrases that express lack of certainty, such as: Appears to Tends to Seems to May indicate Might In some .
