Cannabinoid Based Cancer Treatments Cannabinoids display antitumor properties such as inhibition of cancer cell growth, induction of apoptosis

and blocking the processes involved in tumor progression, such as angiogenesis, and cell migration. These effects might involve several signaling pathways being both cannabinoid receptordependent or independent !isanti "##$%. &hen a person reads the above 'uote they may feel it(s the end of the story. Cannabis kills cancer. But is that really where the story ends) !ro-cannabis researchers and pro-cannabis activists seem to have differing opinions on the answer. *any activists are promoting cannabis that(s high in T+C for any and all types of tumors. ,esearchers suggest that T+C appears to have a great deal of potential in the treatment of a large number of cancer cell lines, but that it(s not always the best cannabinoid to choose for a cancer based treatment. &hy is that) The Expression Level of Cannabinoids Receptors The level of e-pression the number of% of cannabinoid receptors CB,s% in tumor cells appears to be a fundamental factor to the overall effectiveness of cannabinoid based cancer treatments. *ost cannabinoids are CB, activators. These CB,s are (doing all the work( so to speak. .t is not the cannabis or cannabinoids themselves that have anticancer properties, it is the cannabinoids ability to latch onto and activate the appropriate receptors. The activation of these receptors unleashes a cascade of events and mechanisms, some of which are advantages in slowing the progression and inducing apoptosis in tumor cells. CB, activation is fundamental to all cannabinoid based treatments. .f this sounds relatively straight forward, that(s because in a way it is. .n order for cannabinoids to elicit any anticancer effects they must be able to activate the specific CB,s in the tumor cells. The higher the e-pression level of receptors, the greater impact that cannabinoids that activate those receptors have in the treatment. .f there are no receptors to activate in the target area, or the cannabinoids being used are more effective at activating a different receptor, the treatment is likely to be relatively unsuccessful. !isanti "##$% /'ually vital is the awareness that tumor cells with low or undetectable e-pression levels of CB,s are resistant to any anticancer effects that cannabinoids may elicit, and the immunosuppression resulting from the systemic application of cannabinoids have been shown to enhance tumor growth in some cancer cell lines like some types of breast cancer%. !isanti "##$% This paper will attempt to point to some of the research in relation to cancer, the endocannabinoid system /C0%, and natural cannabinoids that activate it. .t may surprise some readers to learn that there is a growing number of legal and natural cannabinoids which originate outside of the cannabis plant. *any of these are cheap, highly available, and share a number of anticancer characteristics to cannabinoids in cannabis via the activation of similar receptors. Receptors/Targets to Consider in Cancer Treatments The primary targets or mechanisms of action in cannabinoid based cancer treatments involve the

activation of CB1 and CB" receptors. .t seems likely that one reason T+C has proven to be relatively effective particularly when combined with other cannabinoids% is based on the fact that it(s a CB1 and CB" activator. +owever, T+C activates CB1 much more efficiently than CB", which is why other cannabinoids might be better options for treatments that would benefit from CB" activation. .n addition to the activation of CB1 and CB", some cannabinoids also activate T,!21 which has been shown to induce apoptosis in tumor cells. 3nother target worthy of mention is 4!,55. 6nlike the other receptors which we are attempting to activate in cancer treatments, 4!,55 activation by natural compounds in the body as well as e-ogenous sources% actually leads to the proliferation of tumor cells, so it is beneficial to block 4!,55 rather than activate it. 7uckily enough there are cannabinoids that block 4!,55. Both CB8 and magnolia officinalis e-tracts block the activation of 4!,55 and slow the proliferation of tumor cells. !isanti "##$% Potentially Useful Cannabinoids in Cancer Treatments 7ist of cannabinoids with some of the relevant receptors that they target9

T+C : CB1;CB" partial activator with CB1 selectivity more potent CB1 activator%, T,!21 activator CB< : CB1;CB" partial activator with CB1 selectivity weaker than T+C% CB4 : CB" activator, 3/3 reuptake inhibitor CB8 : T,!21 activator, 4!,55 blocker, raises 3/3 and "-34 levels, 3/3 reuptake inhibitor CB83 : T,!21 activator 3nandamide 3/3% : CB1;CB" partial activator with CB1 selectivity "-3rachidonoylglycerol "-34% : CB1 partial activator Beta-caryophyllene dietary cannabinoid% : full CB" activator *agnolia officinalis magnolol;honokiol% : CB1;CB" partial activator, 4!,55 blocker /chinacea purpurea new cannabinoid group of alkylamides% : CB" partial activators =ava-=ava yangonin% : CB1 partial activator CB" T+C CB< CB4 beta-caryophyllene m. officinalis echinacea purpurea 3/3 "-34 T,!21 T+C CB8 CB83 4!,55 blockers% CB8 m. officinalis

CB1 T+C CB< m. officinalis kava-kava "-34 3/3

This is not a definitive list, but there might be a few cannabinoids listed that many patients aren(t familiar with.

The first two .(ll point out are 3/3 and "-34. These are endocannabinoids natural cannabinoids in the human body%. These are listed for a few select reasons. They are CB, activators with anticancer characteristics that are naturally produced by the body. That knowledge on its own might not mean much, but coupled with the knowledge of ine-pensive ways of increasing endocannabinoid levels it can be 'uite useful information. 8ietary linoleic acid has been shown to raise levels of both 3/3 and "-34. This is an ine-pensive way to increase the body(s own natural cannabinoids. CB8 also raises levels of both 3/3 and "-34 via >33+ inhibition. .n addition, CB8, CB4, and CBC are all 3/3 reuptake inhibitors which raise 3/3 levels%. <e-t is beta-caryophyllene. Beta-caryophyllene is of value in that it is a full CB" activator that is naturally found in a number of dietary sources. .t can also be found in concentrated levels in a variety of essential oils and nutritional supplements. .n some treatments like some types of breast cancer% CB" activation is likely of greater importance than CB1. ?ne of the most highly researched in regards to anticancer potential is the magnolia officinalis. *agnolia officinalis root bark has been used in Chinese medicine for "### years. .t contains magnolol and honokiol which are both cannabinoids with anticancer characteristics. They activate CB1, CB", and also block 4!,55. 3 point worth mentioning is that they are both known to target apoptosis, which might make their addition to any cannabis based specifically T+C% treatment potentially beneficial. The final two are echinacea purpurea CB" activator% and kava-kava CB1 activator%. These are both relatively new discoveries and there isn(t much information about their specific characteristics in regards to cancer treatment, but as CB1 and CB" are both targets, it might be safe to assume that these have potential as well. Targets/Receptors and Cannabinoids to Consider for pecific Types of Cancer 0o now that we are familiar with our targets receptors% and our weapons cannabinoids% let(s see how this all relates to some types of cancer9 Breast Cancer CB1 e-pression level is lowered CB" e-pression level rises 3/3 and "-34 via CB1 activation reduces cell proliferation T+C immunosupression and non CB, mechanisms have been shown to increase tumor growth and metastisis in some cell lines. T+C induces apoptosis via CB" activation better options for CB" activation% CB8 inhibition and apoptosis via CB" and T,!21 *agnolia officinalis cannabinoids have a great deal of positive research in this treatment T+C might not be the most appropriate cannabinoid for this treatment. ,eader is advised to review research on individual cancer cell lines in relation to this topic in the provided citations.%

!rostate Cancer CB1 and CB" e-pression levels rise T,!21 e-pression levels rise 3/3 via CB1 and CB" inhibits proliferation T+C induces apoptosis via non CB, ?ther cannabinoids have been shown to induce apoptosis via CB1 and CB" *agnolia officinalis cannabinoids have a great deal of positive research in this treatment *any cannabinoids might be well suited 0kin cancer <o information on changes of e-pression levels, but CB" is highly e-pressed in the skin Cannabinoids have been shown to inhibit growth via CB1 and CB" activation Beta-caryophyllene from essential oils can be used in topical applications *agnolia officinalis cannabinoids have a great deal of positive research in this treatment !ancreatic Cancer CB1 and CB" e-pression levels rise T+C induces apoptosis via CB" and ceramide *agnolia officinalis cannabinoids have a great deal of positive research in this treatment *any cannabinoids may be well suited 4lioma and Brain Cancer CB" e-pression levels rise CB1 level of e-pression in brain is high% T+C induces apoptosis via CB1 and CB" T+C reduces proliferation via CB1 T+C inhibits cell invasion via non CB, mechanisms ?ther cannabinoids have been shown to induce apoptosis via CB" and C?@-" inhibition *agnolia officinalis cannabinoids have a great deal of positive research in this treatment T+C is prime candidate 4.;Colon Cancer CB1 e-pression levels rise in gastrocarcinoma CB" e-pression levels rise in colon carcinoma 3/3 induces cell death via C?@-" colorectal carcinoma% 3/3 synergism with 5-fluorouracil ?ther cannabinoids inhibition via non CB, mechanisms ?ther cannabinoids induce apoptosis via CB1 and CB" *agnolia officinalis cannabinoids have a great deal of positive research in this treatment 7oss of CB1 accelerates intestinal tumor growth +ematological Cancer CB" e-pression levels possibly rise 3/3 apoptosis via T,!21 other T,!21 agonists% 3/3 growth inhibition and apoptosis via CB1 and CB" T+C apoptosis via CB" CB8 growth inhibition and apoptosis via non CB,

 !o" Treatment chedule #ight Effect the Efficacy of Treatments .t also seems important to stress the potential relevance of treatment schedules. This is a point that directly relates to the e-pression level of CB,s, which we now understand the role of. The average lifespan of a cannabinoid receptor is around #.5 seconds. Their level of e-pression is constantly in flu-. !atients who have consumed cannabis for e-tended periods of time are familiar with the fact that a AtoleranceA is 'uickly established to cannabinoids. The same is true for patients during cancer treatments. This is in large part due to the level of cannabinoid receptors being lowered and becoming fatigued by the constant e-posure to e-ogenous cannabinoids. .t is also commonly accepted among those who consume cannabis daily that abstaining from cannabis for "B-BChrs lowers a person(s tolerance and increases the effects elicited by cannabinoids. +ow does this relate to cancer treatments) &ell, some research suggests that the efficacy of a cannabinoid based treatment is influenced by the dosing schedule. *ost cancer treatments recommend 1###mg of cannabinoids daily. .s that the most effective schedule) .s it possible that incorporating (off days( and abstaining from cannabinoids might allow the CB,s to recover and increase the efficacy of the overall treatment) 0cientific research indicates this to be the case. 0cott "#1D% 8ue to the reduction of receptor e-pression levels as well as receptor fatigue from overe-posure to CB, activators, it has been shown that it might be significantly more effective to incorporate a (day off( every fourth day in which no cannabinoids are consumed. This allows the e-pression levels of CB,s to rise and allows them to recover from fatigue, in turn this has been shown to increase the efficacy of subse'uent cannabinoid applications. This might be something worth considering for those involved with these types of treatments. 0cott "#1D% Conclusion

This paper isn(t meant to be definitive, but . hope it provides patients with some potentially useful insight into cannabinoid based cancer treatments. The ways in which we discuss the potential of cannabinoids have a direct impact on current treatments. &hen a claim is made that (cannabis cures cancer( that statement taken at face value is potentially dangerous in some scenarios. Cannabis doesn(t kill cancer in the traditional sense, or similar to the way that chemotherapy does. Chemotherapy targets and kills practically everything. That is one reason why cannabinoids offer so much more potential in cancer treatments. Cannabinoids, some of which can be found in cannabis, can be used to coa- the body into slowing these cells down and convincing them to kill themselves in a nonto-ic way. But it(s important to know how to use them by understanding which ones to use. This is gained by identifying the specific receptors that are being targeted. ?nce the targets have been identified a combination of activators can be utiliEed to activate those targets. This message is lost when we speak about the use of cannabis in cancer treatments in an inappropriate manner. Fust talking about this more accurately might increase awareness which might have the potential to increase the efficacy of current cannabinoid based treatments.

Note from author: This paper has not been peer reviewed, nor is the author a licensed professional in the medical field. You're encouraged to read the cited references which are all peer reviewed, and are mostly available to read for free online via Google Scholar. You're also encouraged to share, print, or transmit this paper in anyway you see fit.

3uthor9 Foe 0tone /mail9 cannabinoidbasedtherapeuticsGgmail.com

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