1. Cannabis In Cancer Care
Donald I. Abrams, M.D.
Chief, Hematology-Oncology
Zuckerberg San Francisco General
Professor of Clinical Medicine
University of California San Francisco

3. Cannabinoid1 Receptor
CB1 receptors identified throughout central and peripheral nervous system
Density highest in cingulate gyrus, frontal cortex, hippocampus, cerebellum and basal ganglia
CB1 receptors present in virtually all organs and tissues of the body

5. - Health Canada 2016 Pre-synaptic terminal Ca2+ K+ 4 4 2 2 3 3 6 6
Neurotransmitter
vesicles
Ca2+ K+
THC
Dronabinol
Nabilone 4 4 AA
THC
Dronabinol
Nabilone -
ETA
Ca2+ 2 +
CB1 receptor
STOP
STOP K+
CB1 receptor 2
MAGL 3 3
AEA
2-AG
AEA 6
2-AG
2-AG 6
Post-synaptic
terminal 5
PLD
Neurotransmitter
receptor 5 1
DAGL
NAPE
FAAH
DAG 1
Neurotransmitter
receptor AA
Glycerol
Health Canada 2016

6. Suppression of Neurotransmitter Release
Serotonin (5-HT)
Glutamate
Acetylcholine
GABA
Noradrenaline
Dopamine
D-aspartate
Cholecystokinin
HEALTH CANADA

7. Endogenous Cannabinoid System
Cellular uptake R
Synthesis
Metabolism
Endocannabinoids
CB2 Receptor
CB1 Receptor
CBx Receptor
VR1 Receptor
Signal Transduction
Immune function
Cell proliferation
Inflammation
Pain
Appetite Cognition
Immune function Emesis
Muscle control Neuroexcitability
Pain Reward
IOP Thermoregulation
Pain
Vaso-
dilation
Pain
Inflammation

8. Symptom Management Challenges Associated with Cancer and Its Treatments
Despite therapeutic advancements, cancer and its treatments are associated with a number of difficult symptom management challenges, a few of which are shown here.
For example, some demonstrable weight loss occurs in more than 50% of all cancer patients at some point during their illness.1 Cachexia is present in almost 50% of patients at the time of diagnosis.2 Early satiety is present in approximately 50% of all cancer patients.3 Anorexia is present in an estimated 15% to 40% of cancer patients at diagnosis and in as many as 80% of patients with advanced disease.3 In fact, the syndrome of anorexia and cancer cachexia is considered the most common paraneoplastic syndrome.1 Many factors contribute to the presence of anorexia in cancer patients, including nausea caused by the disease itself or by chemotherapy. Other common conditions include moderate to severe pain, which occurs in approximately one-third of all patients with cancer.4 In addition, anxiety or depression requiring psychological treatment is seen in about one-third of patients with cancer.5 Chemotherapy-induced nausea and vomiting remain two of the most feared effects of cancer treatment. Approximately 30% of patients taking a moderately or highly emetogenic chemotherapy regimen experience acute nausea and vomiting even after antiemetic prophylaxis.6
1. Arnold SM, et al. Paraneoplastic syndromes. In: DeVita VT, et al, eds. Cancer: Principles & Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001:
2. Damsky D. Cachexia in patients with advanced cancer. Clin J Onc Nursing. 2002;6(4):
3. Body JJ. The syndrome of anorexia-cachexia. Curr Opin Oncol. 1999;11(4):
4. Foley KM. Management of cancer pain. In: DeVita VT, et al, eds. Cancer: Principles & Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001:
5. Massie MJ, et al. Psychological issues. In: DeVita VT, et al, eds. Cancer: Principles & Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001:
6. Carlson RH. Better antiemetic regimens still needed. Oncology Times. 2001;23(3):19-23.
1. Arnold SM, et al. In: DeVita VT, et al, eds. Cancer: Principles & Practice of Oncology
2. Damsky D. Clin J Onc Nursing. 2002;6(4):
3. Body JJ. Curr Opin Oncol. 1999;11:
4. Foley KM. In: DeVita VT, et al, eds. Cancer: Principles & Practice of Oncology
5. Massie MJ, et al. In: DeVita VT, et al, eds. Cancer: Principles & Practice of Oncology
6. Carlson RH. Oncology Times. 2001;23(3):19-23.

9. Oral Delta-9 THC: An Approved Drug
Approved in 1986 for N&V from chemoRx; AIDS anorexia in 1992

11. Cannabinoids in Chemotherapy-Induced Peripheral Neuropathy
Activation of CB1 and CB2 receptors suppresses development of vincristine-induced PN in rats
Rahn et al, Br J Pharmacol 2007
In mice receiving daily cisplatin, anandamide plus a FAAH inhibitor attenuated CIPN
Khasabova et al, J of Neuroscience 2012
In mice injected with paclitaxel, CBD pre-treatment aborts CIPN
Ward et al, Br J Pharmacol 2014

13. Pain by Study Day n Day 1 Mean (95% CI) Day 5 Difference (95% CI)*
Overall 21
39.6
(35.8, 43.3)
29.1
(25.4, 32.8)
-10.7
(-14.4, -7.3)
Morphine 10
34.8
(29.4, 40.1)
24.1
(18.8, 29.4)
-11.2
(16.5, -6.0)
Oxycodone 11
43.8
(38.6, 49.1)
33.6
(28.5, 38.6)
-10.3
(14.8, -5.8)
*p<0.001
Abrams et al, Clinical Pharmacology & Therapeutics 2011

14. New Indication for Medicinal Cannabis
Lew et al HemOnc Today 2008

15. Cannabis Oil and Cancer

16. Gliomas Systematic Review
34 in vitro and/or in vivo experimental studies and one pilot human trial included
All but one study showed that cannabinoids selectively kill tumor cells
Antitumor activity
Antiproliferative effects (cell cycle arrest)
Decreased viability
Cell death via toxicity, apoptosis, necrosis, autophagy
Antiangiogenic effects
Antimigratory effects
Machado Rocha et al, J Neurooncology 2014

17. The Lone Human Trial
9 patients with recurrent GBM treated with ug THC intra-tumorally per day x 15d
Treatment was well tolerated
Effect on survival no different from chemo
In vitro, THC inhibited the proliferation and decreased viability of GBM cells from biopsies
Guzman 2006
Later demonstrated that CBD enhanced the inhibitory effects of THC on GBM cell proliferation and survival
Marcu 2010

18. Cannabis-Induced Euphoria
Often described as a “side-effect” of Rx
Is it really an “adverse experience”, particularly in the palliative care setting?
Is a single treatment that increases appetite, decreases nausea and vomiting, relieves pain and improves mood and sleep a potentially useful tool in symptom management?