Medical Marijuana

61. Cannabidiol (CBD) As Antipsychotic

"Our results provide evidence that the non-cannabimimetic constituent of marijuana, cannabidiol, exerts clinically relevant antipsychotic effects that are associated with marked tolerability and safety, when compared with current medications."

Leweke, FM; Piomelli, D; Pahlisch, F; Muhl, D; Gerth, CW; Hoyer, C; Klosterkotter, J; Hellmich, M; and Koethe, D, "Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia," Translational Psychiatry (New York, NY: Nature Publishing Company, March 2012), p. 6.

62. Medical Marijuana - Research - 8-12-10

Substance Abuse and Mental Health Treatment

(Cannabidiol's (CBD's) Potential in Substance Abuse Treatment) "The current study has revealed unique properties of the phytocannabinoid CBD and underscores the contrasting characteristics of the main constituents of cannabis in relation to addiction vulnerability. Compared with the documented effects of THC to enhance heroin self-administration (Solinas et al., 2004; Ellgren et al., 2007), the present data demonstrated that CBD specifically inhibited reinstatement of cue-induced heroin seeking. The specificity of CBD to cue-induced reinstatement was also emphasized by the observation that the compound still inhibited drug relapse behavior in animals extinguished to the environmental context (self-administration chamber) previously associated with heroin. The results are striking given the very selective and protracted effects of CBD."
"Overall, the observations of this study suggest the potential for CBD as a treatment strategy given its specificity to attenuate cue-induced drug-seeking behavior, preferential impact on mesolimbic neuronal populations, and enduring neural actions. Clearly, greater attention needs be given to the potential role of CBD in the treatment of addiction and other mental health disorders."

Ren, Yanhua; Whittard, John; Higuera-Matas, Alejandro; Morris, Claudia V.; and Yasmin L. Hurd, "Cannabidiol, a Nonpsychotropic Component of Cannabis, Inhibits Cue-Induced Heroin Seeking and Normalizes Discrete Mesolimbic Neuronal Disturbances," The Journal of Neuroscience (Washington, DC: Society for Neuroscience, November 25, 2009), Vol. 29, No. 47, pp. 14767 and 14768.

63. Medical Marijuana - Research - 11-14-10

(Cannabidiol (CBD) and Schizophrenia Treatment) "These studies suggest, therefore, that CBD has an antipsychotic-like profile in healthy volunteers and may possess antipsychotic properties in schizophrenic patients, but not in the resistant ones. Confirming this suggestion, a preliminary report from a 4-week, double-blind controlled clinical trial, using an adequate number of patients and comparing the effects of CBD with amisulpride in acute schizophrenic and schizophreniform psychosis, showed that CBD significantly reduced acute psychotic symptoms after 2 and 4 weeks of treatment when compared to baseline. In this trial CBD did not differ from amisulpride except for a lower incidence of side effects (49).
"In conclusion, results from pre-clinical and clinical studies suggest that CBD is an effective, safe and well-tolerated alternative treatment for schizophrenic patients. Future trials of this cannabinoid in other psychotic conditions such as bipolar disorder (50) and comparative studies of its antipsychotic effects with those produced by clozapine in schizophrenic patients are clearly needed."

"Zuardi, A.W.; Crippa, J.A.S.; Hallak, J.E.C.; Moreira, F.A.; and Guimarães, F.S., "Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug," Brazilian Journal of Medical and Biological Research (Ribeirão Preto, Brazil: April 2006), Volume 39, Issue 4, p. 427-428.

64. Cannabinoids and PTSD

"A chart review of patients diagnosed with PTSD who were referred to a private psychiatric clinic suggests that the synthetic cannabinoid, nabilone, has beneficial effects beyond its official indication in regard to abolishing or greatly reducing nightmares that persisted in spite of treatment with conventional PTSD medications.
"The subjects concomitantly received nabilone in addition to the one or more psychiatric medications that they were already taking for 2 years or more. No tolerance to nabilone was observed among the patients. This may indicate its potential longer-term safety and efficacy.
"The author recognizes the limits of this study (e.g., there was no placebo control, the measurements were limited to subjective reports to nightmare changes, the study was on a small number of patients, and there was a selective bias by nature of referrals to a specific clinic from which the patients were selected). Nonetheless, on the basis of these retrospective findings, nabilone appears to be a significant treatment for nightmares in the PTSD population."

Fraser, George A., "The Use of a Synthetic Cannabinoid in the Management of Treatment-Resistant Nightmares in Posttraumatic Stress Disorder (PTSD)," CNS Neuroscience & Therapeutics (Hoboken, NJ: Wiley-Blackwell, Winter 2009), p. 87.

65. Substitution of Cannabis for Other Drugs

"Eighty five percent of the BPG [Berkeley Patients Group] sample reported that cannabis has much less adverse side effects than their prescription medications. Additionally, the top two reasons listed by participants as reasons for substituting cannabis for one of the substances previously mentioned were less adverse side effects from cannabis (65%) and better symptom management from cannabis (57.4%).
"The substitution of one psychoactive substance for another with the goal of reducing negative outcomes can be included within the framework of harm reduction. Medical cannabis patients have been engaging in substitution by using cannabis as an alternative to alcohol, prescription and illicit drugs."

Reiman, Amanda, "Cannabis as a Substitute for Alcohol and Other Drugs," Harm Reduction Journal (London, United Kingdom: December 2009).

66. Medical Cannabis Legalization and Adolescent Cannabis Use

"Indeed, all 11 states that have passed medical marijuana laws ranked above the national average in the percentage of persons 12 or older reporting past-month use of marijuana in 1999, as shown in Table 2. It is at least possible, however, that this analysis confuses cause with effect. It is logical to assume that the states with the highest prevalence of marijuana usage would be more likely to approve medical marijuana programs, because the populations of those states would be more knowledgeable of marijuana’s effects and more tolerant of its use.

"It is also the case that California, the state with the largest and longest-running medical marijuana program, ranked 34th in the percentage of persons age 12-17 reporting marijuana use in the past month during the period 2002-2003, as shown in Table 1. In fact, between 1999 and 2002-2003, of the 10 states with active medical marijuana programs, five states (AK, HI, ME, MT, VT) rose in the state rankings of past-month marijuana use by 12- to 17-year-olds and five states fell (CA, CO, NV, OR, WA).111 Of the five states that had approved medical marijuana laws before 1999 (AK, AZ, CA, OR, WA), only Alaska’s ranking rose between 1999 and 2002-2003, from 7th to 4th, with 11.08% of youth reporting past-month marijuana use in 2002-2003 compared with 10.4% in 1999. No clear patterns are apparent in the state-level data. Clearly, more important factors are at work in determining a state’s prevalence of recreational marijuana use than whether the state has a medical marijuana program."

Eddy, Mark, "Medical Marijuana: Review and Analysis of Federal and State Policies," Congressional Research Service (Washington, DC: March 31, 2009), p. 32.

67. Adolescents - Usage - 12-24-09

(Non-Recreational Adolescent Marijuana Use) "The findings of this study provide one of the first in-depth descriptions of youths' use of marijuana for non-recreational purposes, adding to the growing body of research on the use of drugs to self-medicate among young people. Teens involved in regular and long-term use of marijuana for relief constructed their use of marijuana as essential to feeling better or 'normal' in situations where they perceived there were few other options available to them. Unlike the spontaneity typically involved in recreational use, these youth were thoughtful and prescriptive with their marijuana use – carefully monitoring and titrating their use to optimize its therapeutic effect. The findings also point to important contextual factors that further support youth's use of marijuana for relief that extend beyond the availability of marijuana and dominant discourses that construct marijuana as a natural product with medicinal properties."

Bottorff, Joan L , Johnson, Joy L, Moffat, Barbara M, and Mulvogue, Tamsin, "Relief-oriented use of marijuana by teens," Journal of Substance Abuse Treatment, Prevention, and Policy (Vancouver, BC: April 2009), doi:10.1186/1747-597X-4-7.

68. Impact of Medical Marijuana Laws (MMLs) on Cannabis Use by Youth

"We replicated the findings of Wall et al. (2) that marijuana use was higher in states that have passed MMLs, and our analysis suggests this is unlikely to be a causal association. Our difference-in-differences estimates suggest little detectable effects of passing MMLs on marijuana use or perceived riskiness of use among adolescents or adults, which is consistent with some limited prior evidence on arrestees and emergency department patients (17). Future analyses that take advantage of additional policy changes may provide further evidence on this question, but our results suggest that such analyses should adequately control for potential confounding by unmeasured state characteristics."

Sam Harper, Erin C. Strumpf, and Jay S. Kaufman, "Do Medical Marijuana Laws Increase Marijuana Use? Replication Study and Extension," Annals of Epidemiology, March 2012 (Vol. 22, Issue 3, Pages 207-212, DOI: 10.1016/j.annepidem.2011.12.002).

69. Youth Medical Marijuana Use and Unmet Health Needs

"Of key importance in the findings are the unmet health needs of these youth. Health issues such as depression, insomnia, and anxiety were significant problems that interfered with these youths' ability to function at school, maintain relationships with family and friends, and feel that they could live a normal life. The level of distress associated with these health concerns, along with the lack of effective interventions by heath care providers and family members appeared to leave them with few alternatives. Researchers have reported that when adolescents in rural communities experience barriers to seeking health care, they think they can take care of the problems themselves [30]. Similarly, our study participants believed that their best option was to assume responsibility for treating their problems by using marijuana. Unpleasant side effects with prescribed medications and long, ineffective therapies resulted in little hope that the medical system could be counted on as beneficial. In contrast, marijuana provided these youth with immediate relief for a variety of health concerns. Nevertheless, the regular use of marijuana put youth at risk. Cannabis use has been identified as a risk factor for mental illness such as psychosis, schizophrenia [21,31,32] and psychiatric symptoms such as panic attacks [33]. Teens who smoked marijuana at least once per month in the past year were found to be three times more likely to have suicidal thoughts than non-users [34], and there is evidence that exposure to cannabis may worsen depression in youth [35]. Marijuana use among youth has also been associated with other substance use and school failure [36]. What is interesting is that the findings of this study suggest that youth have little awareness of some of these risks; rather, some are using marijuana to counteract these very problems (e.g., depression, school failure). Teens' perceptions that their health concerns were not addressed suggest that more attention is needed to assess these issues and ensure that other options are available to them. Parents and health care providers need to make a concerted effort to not only understand the pressures and influences on youth [37], but also gain a better understanding of the effect of youths' health problems on their ability to engage in healthy lifestyle choices."

Bottorff, Joan L , Johnson, Joy L, Moffat, Barbara M, and Mulvogue, Tamsin, "Relief-oriented use of marijuana by teens," Journal of Substance Abuse Treatment, Prevention, and Policy (Vancouver, BC: April 2009), doi:10.1186/1747-597X-4-7.

70. Youth Medical Marijuana Use and Reasons for Self-Medication

"Underlying problems related to youth health concerns also need to be addressed. In many situations, the participants' symptoms appeared to be directly related to their life circumstances. Along with the challenges inherent in being an adolescent in today's complex world, some teens were also trying to deal with significant losses (death of a close friend or family member), extremely difficult family relationships, disappointments with friends, school and sports, and a fragile family and peer support network. The risk of substance use increases substantially when youth are attempting to deal with these kinds of situations in isolation. Although marijuana provided the youth with temporary relief, the underlying situation often went unattended – leading the teens into a regular pattern of use. Appropriate guidance and targeted support from counselors and health care providers must be sensitive to meeting the needs of youth as they work through such situations and life altering events. In addition, adults working with youth must find better ways to talk with young people about how they are coping with their health issues, including their marijuana use. Based on the experiences of youth in this study, there is a wide range of support that may benefit youth including counseling, stress management, social skills training, anger management, study skills, pain management, and sleep hygiene. The youth in this study had minimal access to these types of resources."

Bottorff, Joan L , Johnson, Joy L, Moffat, Barbara M, and Mulvogue, Tamsin, "Relief-oriented use of marijuana by teens," Journal of Substance Abuse Treatment, Prevention, and Policy (Vancouver, BC: April 2009), doi:10.1186/1747-597X-4-7.

71. Effects of State Medical Marijuana Laws (MMLs) on Youth Marijuana Use

"We found no evidence of intermediate-term effects of passage of state MMLs on the prevalence or frequency of adolescent nonmedical marijuana use in the states evaluated, with 2 minor exceptions. From 2003 through 2009, adolescent lifetime prevalence of marijuana use and frequency of daily marijuana use decreased significantly in Montana, as compared with a more modest decrease in lifetime prevalence and an increase in daily frequency observed in Delaware (Ps = .03). These 2 statistically significant findings do not appear to represent real effects. Our difference-in-differences study design involved 40 planned comparisons (before---after differences in treatment vs comparison states), and naturally 2 significant results (at the P < .05 level) of a possible 40 can be expected according to chance alone.
"Moreover, the pattern is not consistent with an effect of MMLs. A significant effect was found for lifetime marijuana use but not past-month marijuana use. Self-reported lifetime use requires a much longer recall period than past-month use and is characterized by higher measurement error.13 Also, one would expect the 30-day use measure to be more sensitive than lifetime use to the effects of a change in MMLs, because most of the period covered by respondents’ lifetime reports occurred before passage of an MML.
"Finally, the significant increase in daily marijuana use was observed for the comparison state of Delaware, which had not enacted an MML during the years under evaluation, whereas the frequency of daily marijuana use in Montana decreased. This is the opposite of
what would be expected if MMLs had the deleterious effect of increasing the frequency of nonmedical marijuana use.
"Conversely, the significant effects observed were found between the 2 states that differed the most on the timing of MML enactment, maximizing the length of the follow-up period. Hence, it is reasonable to suspect that enacting an MML may influence the prevalence and frequency of adolescent nonmedical marijuana use half a decade later, despite no evidence of more proximal effects."

Sarah D. Lynne-Landsman, PhD, Melvin D. Livingston, BA, and Alexander C. Wagenaar, PhD, "Effects of State Medical Marijuana Laws on Adolescent Marijuana Use," American Journal of Public Health, June 13, 2013.
Abstract at: http://ajph.aphapublications.o...

72. Medical Marijuana - Dronabinol - 2-26-11

Marinol and Dronabinol

(Dronabinol) "Dronabinol (?-9-tetrahydrocannabinol [THC]) is an alternative treatment for nausea and vomiting caused by chemotherapy. THC is the principal psychoactive component of marijuana. Its mechanism of antiemetic action is unknown, but cannabinoids bind to opioid receptors in the forebrain and may indirectly inhibit the vomiting center. Dronabinol is administered in doses of 5 mg/m2 po 1 to 3 h before chemotherapy, with repeated doses q 2 to 4 h after the start of chemotherapy (maximum of 4 to 6 doses/day). However, it has variable oral bioavailability, is not effective for inhibiting the nausea and vomiting of platinum-based chemotherapy regimens, and has significant adverse effects (eg, drowsiness, orthostatic hypotension, dry mouth, mood changes, visual and time sense alterations). Smoking marijuana may be more effective. Marijuana for this purpose can be obtained legally in some states. It is used less commonly because of barriers to availability and because many patients cannot tolerate smoking."
1. "Dronabinol, the active ingredient in MARINOL® (dronabinol) Capsules, is synthetic delta-9-tetrahydrocannabinol (delta-9-THC). Delta-9-tetrahydrocannabinol is also a naturally occurring component of Cannabis sativa L. (Marijuana)."
2. "Dronabinol is a name of a particular isomer of a class of chemicals known as tetrahydrocannabinols (THC). Specifically, dronabinol is the United States Adopted Name (USAN) for the (-)-isomer of [Delta]\9\-(trans)- tetrahydrocannabinol [(-)-[Delta]\9\-(trans)-THC], which is believed to be the major psychoactive component of the cannabis plant (marijuana)."
3. "A United States Adopted Name (USAN) is the "US generic name for any compound to be used as a drug."
4. Dronabinol is the generic name for THC or tetrahydrocannabinol.

Chabner, Bruce A. and Thompson, Elizabeth Chabner, "Management of Adverse Effects," The Merck Manual (Whitehouse Station, N.J: Merck & Co. Inc., July 2009), Section: Hematology and Oncology, Chapter: Management of Adverse Effects, Nausea and Vomiting.
"MARINOL® (dronabinol) Capsules," (Abbott Laboratories: Abbott Park, IL, July 2006), pp. 11.
Federal Register, "Listing of Approved Drug Products Containing Dronabinol in Schedule III," Vol. 75, No. 210, Monday, November 1, 2010, pp. 67054 to 67059.
"United States Adopted Name," The Bantam medical dictionary, p. 685.

73. Marinol (Synthetic THC

MARINOL® (dronabinol) Capsules
"After oral administration, dronabinol has an onset of action of approximately 0.5 to 1 hours and peak effect at 2 to 4 hours. Duration of action for psychoactive effects is 4 to 6 hours, but the appetite stimulant effect of dronabinol may continue for 24 hours or longer after administration.
"MARINOL Capsules is indicated for the treatment of:
"1. anorexia associated with weight loss in patients with AIDS; and
"2. nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments.
"A cannabinoid dose-related “high” (easy laughing, elation and heightened awareness) has been reported by patients receiving MARINOL® Capsules in both the antiemetic (24%) and the lower dose appetite stimulant clinical trials (8%)
"MARINOL Capsules is one of the psychoactive compounds present in cannabis, and is abusable and controlled [Schedule III (CIII)] under the Controlled Substances Act. Both psychological and physiological dependence have been noted in healthy individuals receiving dronabinol, but addiction is uncommon and has only been seen after prolonged high dose administration.
"Chronic abuse of cannabis has been associated with decrements in motivation, cognition, judgement, and perception. The etiology of these impairments is unknown, but may be associated with the complex process of addiction rather than an isolated effect of the drug. No such decrements in psychological, social or neurological status have been associated with the administration of MARINOL Capsules for therapeutic purposes.
"In an open-label study in patients with AIDS who received MARINOL Capsules for up to five months, no abuse, diversion or systematic change in personality or social functioning were observed despite the inclusion of a substantial number of patients with a past history of drug abuse.
"Signs and symptoms following MILD MARINOL Capsules intoxication include drowsiness, euphoria, heightened sensory awareness, altered time perception, reddened conjunctiva, dry mouth and tachycardia; following MODERATE intoxication include memory impairment, depersonalization, mood alteration, urinary retention, and reduced bowel motility; and following SEVERE intoxication include decreased motor coordination, lethargy, slurred speech, and postural hypotension. Apprehensive patients may experience panic reactions and seizures may occur in patients with existing seizure disorders.
Note: Marinol® is now marketed by Abbott Laboratories.

"MARINOL® (dronabinol) Capsules," (Abbott Laboratories: Abbott Park, IL, July 2006), pp. 1, 2, 6, 9, 10, 11, and 13.
Abbott Marinol® pricing as of 2/27/11:

74. Rescheduling

Other Laws & Policies

"Medical experts emphasize the need to reclassify marijuana as a Schedule II drug to facilitate rigorous scientific evaluation of the potential therapeutic benefits of cannabinoids and to determine the optimal dose and delivery route for conditions in which efficacy is established.2 This research could provide the basis for regulation by the Food and Drug Administration. Current roadblocks to conducting clinical trials, however, make this more rational route of approval unlikely and perpetuate the development of state laws that lack consistency or consensus on basic features of an evidence-based therapeutic program."

Hoffman, Diane E., and Weber, Ellen, "Medical Marijuana and the Law," New England Journal of Medicine (Boston, MA: Massachusetts Medical Society, April 22, 2010), Vol. 362, No. 16, p. 1457.

75. Legalizing Without Congress

"Not surprisingly, the Obama Administration would have been more successful had it simply legalized medical marijuana.143 In fact, the CSA [Controlled Substances Act] authorizes the Attorney General to do so, in consultation with the Secretary of Health and Human Services and the DEA.144 In other words, the President would not need the consent of the Congress to make this, more fundamental change to federal law."

Miklos, Robert A., "A Critical Appraisal of the Department of Justice's New Approach to Medical Marijuana" (February 23, 2011). Stanford Law & Policy Review, Vol. 201, p. 101, 2011 ; Vanderbilt Public Law Research Paper No. 11-07, pp. 665-666.

76. NIDA's Federal Medical Cannabis Program

"It is a judicial fluke that the National Institute on Drug Abuse has provided medical marijuana to a handful of patients (never more than 32, currently 4 surviving) as the outcome of the settlement in a lawsuit pressed in 1976 by a man with cannabis-responsive glaucoma. That settlement became the basis for the FDA’s Compassionate Investigational New Drug Study program for patients with marijuana responsive conditions. No patient has been enrolled since 1992, when the George H. W. Bush administration suspended new registration in reaction to a large influx of applications from AIDS patients."

Bostwick, J. Michael, "Blurred Boundaries: The Therapeutics and Politics of Medical Marijuana," Mayo Clinic Proceedings (Rochester, MN: Mayo Clinic, February 2012), Vol. 87, No. 2, p. 182.

77. Current Scheduling of Cannabis

Cannabis (marijuana) is listed in Schedule I of the 1970 Controlled Substance Act. Schedule 1 classification is supposed to mean: "(A) The drug or other substance has a high potential for abuse. (B) The drug or other substance has no currently accepted medical use in treatment in the United States. (C) There is a lack of accepted safety for use of the drug or other substance under medical supervision."

U.S. Code. Title 21, Chapter 13 -- Drug Abuse Prevention and Control -- Section 812, Schedules of Controlled Substances, p. 384.

78. Medical Marijuana - 4-11-10

(History) "For most of American history, growing and using marijuana was legal under both federal law and the laws of the individual states. By the 1840s, marijuana’s therapeutic potential began to be recognized by some U.S. physicians. From 1850 to 1941 cannabis was included in the United States Pharmacopoeia as a recognized medicinal.4 By the end of 1936, however, all 48 states had enacted laws to regulate marijuana.5 Its decline in medicine was hastened by the development of aspirin, morphine, and then other opium-derived drugs, all of which helped to replace marijuana in the treatment of pain and other medical conditions in Western medicine.6"

Eddy, Mark, "Medical Marijuana: Review and Analysis of Federal and State Policies," Congressional Research Service (Washington, DC: March 31, 2009), p. 1.

79. Exceptions to Federal Ban

"Only two limited exceptions to the federal ban on marijuana have been made. The first, a compassionate use program created under President Carter, is superficially analogous to extant state medical use programs; it allows patients to use marijuana legally for therapeutic purposes. The marijuana for the program is supplied by a federally approved grow-site at the University of Mississippi (the only federally approved grow-site in the United States). However, the program stopped accepting new applications in 1992, and only eight (yes, eight) patients currently receive marijuana through it. Over its entire history, only thirty-six patients have been enrolled.52 The second and only other way to obtain marijuana legally under federal law is by participating in an FDA-approved research study. But since the federal government approves so few marijuana research projects—eleven since 200053—only a small fraction of the population that currently qualifies for state exemptions could participate."

Miklos, Robert A., "On the Limits of Supremacy: Medical Marijuana and the States’ Overlooked Power to Legalize Federal Crime," Vanderbilt Law Review (Nashville, TN: Vanderbilt University Law School, March 9, 2009), p. 113.

80. Medical Marijuana - Law & Policy - 7-13-12

"Although Raich established Congress’s constitutional authority to enact the existing federal prohibition on marijuana, principles of federalism prevent the federal government from mandating that the states support or participate in enforcing the federal law. While state resources may be helpful in combating the illegal use of marijuana, Congress’s ability to compel the states to enact similar criminal prohibitions, to repeal medical marijuana exemptions, or to direct state police officers to enforce the federal law remains limited. The Tenth Amendment likely prevents such an intrusion into state sovereignty."

Garvey, Todd, "Medical Marijuana: The Supremacy Clause, Federalism, and the Interplay Between State and Federal Laws," Congressional Research Service (Washington, DC: Library of Congress, March 6, 2012), p. 5.