Cannabinoids Effect on Food Intake_Why Pot Gives You Munchies

Cannabinoids Effect on Food Intake: Why Pot Gives You Munchies
Neel Patel
Molecular and Cellular Biology, University of Illinois at Urbana-Champaign
Dr. Thomas Anastasio
Molecular and Cellular Biology
December 9, 2015

Cannabinoids Effect on Food Intake: Why Pot Gives You Munchies 1
Abstract
This thesis aims to provide a clearer picture of the regulatory mechanisms and pathways
associated with cannabinoids that are involved in the control of the food intake system. This
work was carried out by review of previously published results followed up with a synthesis of
these findings. Expanding upon my foundation of knowledge about the food intake system,
here I provide a framework that can be further expanded upon and utilized to propose
potential drug targets to combat obesity.
Introduction
Food intake is a daily process which we undergo without much thought, however there
are many factors that affect this decision. We often find ourselves eating out of hunger, to
supplement our bodies with proper nutrients, or in other cases, simply due to social setting.
However, in some cases, reward associated food-intake overrides the nutrient and energy
balance, a leading cause in the epidemic known as obesity. Over the last two years I have been
working towards a better understanding of how the decision to eat is made and how the neural
network is coordinated to carry out this action, as well as to terminate a meal. We can use
available data to construct data driven computational models. Applying computational biology
methods, we will be able to determine the factors that play important roles in the obesity
problem. Though through the process of this thesis there will be no computational biology
implemented, the information necessary to begin computing will be provided.
In my research thus far, I have been able to study many pathways considered to be
essential in the control of food intake. In making the decision to pursue a senior thesis I wanted
to explore a control mechanism that has been studied less. This desire, along with additional

guidance, led me to the endocannabinoid system (ECS). The ECS has been widely found to play
a role in stimulating food intake, producing an orexigenic (i.e. an increase in food intake) effect.
A cannabinoid, Δ-tetrahydrocannabinol (Δ-THC) is the active component in marijuana, which is
also known to stimulate appetite. Though I have never ingested drugs, the ongoing debate on
legalization of marijuana and the relevance to the food intake system led me to choose to
pursue this enticing topic. I will be able to shed some light on one of the effects of marijuana
while expanding the observed neural network for food intake control.
Previous research reveals an extensive and synergistic network in the modulation of
energy intake and metabolism. Among key mediators are proopiomelanocortin (POMC)
neurons in arcuate nucleus of the hypothalamus are known to produce an anorexigenic (i.e. a
decrease in food intake) effect3. This pathway has been extensively studied as one of the key
regulators of food intake. POMC neuronal activity is known to be mainly regulated by leptin, a
key hormone in the energy homeostasis system. It has been noted that leptin receptors
become unresponsive to sustained high levels of leptin in circulation, also known as leptin
resistance. Leptin resistance has been highly implicated as a factor contributing to obesity7.
There is a wealth of available research results on leptin's role in inhibiting food intake, however
due to the complex nature of the system there is yet to be an effective, long-term solution to
the obesity problem. Ghrelin is yet another hormone implicated in the control of food intake. It
plays an orexigenic role, opposing the action of leptin within the system. There are many other
hormones and neuropeptides that contribute to the regulation of food intake such as
neuropeptide Y (NPY), α-melanocyte stimulating hormone (α-MSH), cocaine-and-amphetamine
regulated transcript (CART), and corticotropin releasing hormone (CRH) to name a few. These

hormones and others come together to regulate the complex neural network that modulates
both short and long term food intake. The endogenous cannabinoids play an important role in
this complex process.
Previous research indicates that endocannabinoids (endogenous cannabinoids) relay
their signals through cannabinoid-1 receptors (CB1R)25. However, it is yet to be determined the
exact mechanism through which the ECS regulates the food-intake control system. In order to
further understanding in this field we must make determinations of how endocannabinoids are
able to relay messages from both peripheral and central hormone regulation through various
mechanisms. It will also be pivotal to determine the duration of control via the ECS. Through
my literature review research I found that the ECS integrates both anorexigenic and orexigenic
signals and ultimately induces food intake. Through this research I investigated both a short
and long term effect, though each also has a dose and time-dependent effect. I believe that my
research creates a clearer image of the ECS within the complex regulatory mechanisms of
appetite regulation.
Experimental Approach
The approach I took in this thesis differs a lot from the typical wet-lab type of research.
Working with Dr. Anastasio I was able to create the necessary timeline and plan to move
forward with my thesis. Most research is driven by data gathered through one's own lab work,
however I have taken an alternative and less common approach. Rather than running my own
laboratory tests I worked to incorporate the findings from many articles that have already been
published. The process involved the utilization of review articles, sent to me by MIP graduate
student Shayan Tabe Bordbar, to build a foundation upon which I can expand my knowledge.

The review articles also served to help in the discovery of primary source articles which were
also approved by Shayan. The University of Illinois research database was instrumental in
locating published articles that were relevant to the problem at hand. These primary source
articles provided information on specific interactions. Each article focused on a different aspect
of the neural network that regulates food intake but, very few attempted to synthesize their
findings with other findings in the field. Through the course of the thesis I put together each
piece of information much like putting together pieces of a puzzle.
Upon accumulating a list of primary sources I was able to move onto the central part of
the thesis. Through this process I was able to utilize many articles in order to extrapolate key
regulatory mechanisms and the pathways in which they were implicated. Gathering this
information however was only the first step in this process. Though each article served its own
purpose, the true challenge was in bringing each piece of information together. This was done
by organizing the information from each paper into its own category. The initial breakdown I
chose in order to better approach the question at hand was general, peripheral, and central
effects. This was followed by extrapolation as to how these systems may connect to each
other. Prior to bringing each of these works together I had to summarize the findings of each
individually. By summarizing each article individually I am able to gain a more firm
understanding before moving further to synthesize all of this information together. This firm
understanding is necessary in order to draw rational conclusions. A well-grounded
interpretation of these articles will guide this field of research forward by making connections
between previously isolated results and creating a clearer picture as to how this neural network
regulates food intake.

Results
General Effects of Cannabinoids on Food Intake
Before diving into specific mechanisms through which cannabinoids regulate food intake
we must examine general effects. This includes regulation of both cannabinoid levels and food
intake that occur on a large scale basis. The principal areas of breakdown within this category
will be general effects through CB1Rs, the effects of marijuana and its active components, the
opioid-cannabinoid interaction, and leptin-cannabinoid interactions. These general effects may
be further incorporated as I move forward with the findings of this thesis.
Cannabinoids have been noted to play a role in the regulation of food intake and are
considered a potential target for anti-obesity drugs. A specific CB1R antagonist, SR141716, has
been studied extensively as a potential treatment. Through experimentation, SR141716 has
been found to decrease both the body weight and energy intake of high fat diet (HFD)-fed
mice25. The reduction in energy intake indicates a decrease in food intake in animals. Such a
decrease can be attained in many ways including decrease in meal size, meal frequency, or
even meal duration. This decrease in food intake is dose-dependent27. At lower doses
SR141716 significantly decreases food intake, but these effects are diminished at higher doses.
It was also determined that treatment with CB1R antagonist was able to reverse the decrease
in sensitivity to, and increase the levels of, insulin. Both of these effects are typically associated
with obesity. Upon further investigation it was concluded that SR141716 produced only a
transient effect on food intake, but a sustained effect on body weight25. This finding suggests
that reduction of food intake contributes to the initial decrease of body weight, but does not
produce the sustained decrease. The sustained decrease of body weight was a result of

increased energy expenditure. To ensure these effects were a direct result of SR141716 action
at CB1Rs, there was a comparison in food intake of both CB1-knockout (CB1-KO) and wild-type
(WT) mice. It was determined that SR141716 was not able to induce any difference in food
intake in CB1-KO mice27. CB1R antagonist SR141716 caused a transient decrease in food intake
only in the presence of CB1Rs, suggesting that activation of CB1Rs by cannabinoids causes an
increase in food intake.
One cannabinoid of particular interest is the active component of marijuana; Δ-THC.
Both intraperitoneal injection of Δ-THC in mice and marijuana smoking in humans have been
shown to stimulate appetite. More specifically, Δ-THC has been shown to preferentially
increase food intake for high-fat and sweet (HFS) food items5,16. Measured on a more detailed
time scale, Δ-THC injection in mice was shown to increase feeding of standard chow, HFD, and
HFS, however HFD feeding was still greatest one hour after injection. As the experiment
reached the two hour mark there was a clear preference shown for both HFD and HFS over
standard chow16. There was also an increase in overall daily food intake with administration of
Δ-THC through smoking marijuana. In comparison to placebo-administered control humans, Δ-
THC produced an increase of anywhere from 100 to 700 kcal daily5. As was also noted in mouse
experiments, here they showed that humans also preferred solid, sweet foods. Upon more
detailed examination it was determined that this increase in daily food intake was not a result
of calories ingested through meals but rather through snacks and furthermore was a direct
result of an increase in the number of snacking occasions5. Through the results of these
experiments we can extrapolate that Δ-THC, a cannabinoid and the active component of

marijuana, stimulates appetite and increases food intake by increasing the frequency of solid,
sweet snack occurrences.
Both cannabinoids and opioids are known to induce food intake, but very little work has
been done to determine if they work together. That they do interact was confirmed by
administration of both opioid and cannabinoid antagonists, which produced an anorexigenic
effect. Interestingly, it was determined that the reduction in food intake detected through
administration of opioid and cannabinoid antagonists was greater than the sum of antagonizing
each receptor individually15. This information suggests that opioids and cannabinoids work
together and increase food intake in a synergistic manner.
Leptin has been heavily implicated in the regulation of food intake. As noted previously,
leptin regulates many factors in order to reduce food intake. This includes an upregulation of
anorexigenic neuropeptides such as α-MSH and downregulation of orexigenic factors such as
NPY. Leptin also regulates endocannabinoid levels. Acute treatment with leptin reduces
hypothalamic levels of the two main endocannabinoids, which are anandamide (AEA) and 2-
arachidonoylglycerol (2-AG), in order to decrease food intake7. Endocannabinoid and leptin
signals are both integrated in the appetitive neural circuit. Cannabinoids increase feeding
through CB1Rs in the lateral hypothalamus, which inhibit gamma-aminobutyric acid (GABA)
transmission to perifornical melanin-concentrating hormone (MCH) positive neurons. Leptin is
able to disrupt this orexigenic signal of endocannabinoids through downregulation of voltage-
gated calcium currents. This downregulation of cellular calcium levels also disrupts
endocannabinoid synthesis12. In contrast to wild type animals which have increased leptin
levels following standard (STD) diet, CB1R-KO mice show decreased leptin levels after eating

the same food. It is also worth noting that in CB1R-KO mice there is a reduction in body weight
after 14 weeks on STD diet26. On this diet, CB1R-KO mice show a reduction in body weight
compared to WT animals that is further reduced when injected with leptin. This result likely
suggests a mechanism through which cannabinoids are acting against leptin's anorexigenic
effects. Though CB1R-KO mice ate less than WT mice (not of statistical significance), both
consumed high levels of STD food but CB1R-KO mice are leaner than WT controls. This suggests
that the reduction in weight gain and fat storage is likely to be related to metabolic changes26.
Central Effects
Cannabinoids exert many of their effects through central pathways within the brain.
One of the key regions of regulation is the forebrain, but the ventral tegmental area (VTA) of
the midbrain also plays a role. The forebrain region most closely associated with food intake is
the hypothalamus.
Endocannabinoid levels are known to fluctuate relative to the level of satiation. Both Δ-
THC and AEA are able to induce overeating in rats, which is defined as feeding beyond satiation.
It has been noted that in control animals, AEA levels are increased in limbic forebrain and 2-AG
levels are increased in the hypothalamus during periods of food deprivation. Both
endocannabinoids are found to be increased in food-deprived rats, while 2-AG levels decrease
during feeding14. The decrease in 2-AG levels during feeding indicates 2-AG contributes to food
intake initiation rather than maintenance.
While feeding states cause fluctuation in cannabinoid levels, cannabinoid levels are also
able to regulate the levels of some of the neuropeptides involved in food-intake. Of particular
interest, cannabinoids regulate levels of NPY and ß-endorphins in the hypothalamic arcuate

nucleus (ARC) of rats. This regulation is key because both NPY and ß-endorphins stimulate food
intake. Presence of CB1R-antagonists decreased NPY and ß-endorphin levels while CB1R
agonists have the opposite effect1. However, CB1R antagonists decreased food intake to the
same level in both WT and NPY-KO mice. This indicates that CB1R effects are not mediated
through NPY despite NPY levels being modulated by cannabinoids.
Cannabinoid-1 receptor messenger ribonucleic acid (mRNA) is greater in the
ventromedial hypothalamus (VMH) than in other hypothalamic regions11. Injection of
anandamide directly into the VMH dose-dependently causes an increase in food intake11. It
was once again noted that the endocannabinoid effect did not persist once the meal was
initiated, consistent with the idea that they are necessary only for initiation and not
maintenance of the meal.
It is necessary to keep in mind that there may be a difference in the effects of
endogenous cannabinoids, AEA, and exogenous cannabinoids, Δ-THC. Administration of either
Δ-THC or AEA in rats leads to hypothermic temperatures relative to control19. The hypothermic
temperature indicates that both Δ-THC and anandamide play a role in thermogenic control,
likely through energy expenditure regulation. This was further confirmed by the locomotor test
indicating that each of these cannabinoids significantly decrease locomotor activity. While Δ-
THC and AEA both equally activate the lateral septum and paraventricular nucleus (PVN), Δ-THC
caused significantly greater activation in the nucleus accumbens (NAc), caudate, putamen, and
central nucleus of the amygdala (CeA)19. The critical difference is that Δ-THC is able to
stimulate dopamine (DA) release into the NAc while AEA is not able to do so. This difference in
activation may be a result of two different CB1-receptor subtypes: CB1 and CB1A. While

anandamide shows an equal affinity for both receptor subtypes, Δ-THC shown significantly
greater affinity for the CB1 receptor19. The disparity in receptor affinity can lead to variance in
activation through many different brain regions as is noted above.
Forebrain signaling of cannabinoids plays a role in the regulation of energy metabolism.
Uncoupling protein-1 (UCP1) is a proton carrier within mitochondria that help mediate energy
metabolism. UCP1 mRNA levels are increased in the brown adipose tissue (BAT) of mice that
lack CB1Rs, which is indicative of increased thermogenic capacity13,22. Furthermore, a decrease
in 2-AG levels in the forebrain is associated with an increase in energy dissipation13. This
suggests that more energy is used for the same tasks in CB1R-KO mice relative to WT.
Cannabinoid levels may also be responsible for lipogenesis, allowing alteration in fat mass. In
CB1R-KO mice there is a marked reduction in percentage of fat mass with a slight increase in
the percentage of lean mass both in comparison to WT mice2. These results suggest that CB1Rs
influence energy metabolism through UCP1 and play a role in regulation of fat content.
POMC neurons within the hypothalamus are able to regulate endocannabinoid levels.
These POMC neurons are the source of the calcium-dependent endocannabinoid production
discussed previously in regards to decreased GABAergic transmission8. This is evident due to
the constitutive release of endocannabinoids in the ARC, more specifically localized in POMC
neurons. The endocannabinoids act retrogradely to inhibit presynaptic GABA release in order
to upregulate endocannabinoid levels in the ARC8. This suggests that GABA release may serve
as a tonic inhibitory mechanism for ARC cannabinoid levels. Cannabinoids are able to stimulate
release of certain neuropeptides from POMC neurons that would otherwise not be secreted.
POMC neurons are traditionally anorexigenic and rely, in part, on the release of α-MSH for this.

However, CB1Rs in association with mitochondrial uncoupling protein-2 (UCP2) are able to
promote ß-endorphin release in place of α-MSH17. ß-endorphin is known to promote feeding.
CB1R activation is able to inhibit glutamatergic input to the ARC. This will selectively decrease
the excitability of ARC POMC neurons and thus promote food intake9.
Cannabinoids also regulate other hormones and systems. Cannabinoid activation of
CB1Rs decreases GABA release and by decreasing inhibition of MCH neurons causes an indirect
excitation of MCH neurons10. Interestingly, the decrease in both GABAergic and glutamatergic
transmission should, but do not cancel out each other’s effects. This is something that was not
addressed in results I read and needs to be further studied. Anandamide is also implicated in
regulation of hypocretin. A reduction in glutamate release decreases the excitation, and thus
inhibits, hypocretin neurons10. This system was further studied and it was determined that the
central melanocortin system is not necessary for the cannabinoid-induced increase in food
intake. This was confirmed due to the lack of MCH stimulation in response to intra-VTA
cannabinoid injection23. In association with meal termination, however, there was a noted
increase in DA within NAc. This implies that cannabinoids rely on DA release to terminate a
meal and promote satiety23. Endocannabinoids also regulate glutamatergic transmission in the
VTA. It has been suggested that endocannabinoids are produced and released during the
depolarization of DA cells and will act retrogradely onto presynaptic CB1Rs to reduce glutamate
release20. This reduction in glutamate can be associated with the decrease in excitability of
many neurons.
Ghrelin is another important orexigenic hormone. Ghrelin's effect is mediated through
the central activation of the ECS18. Ghrelin is known to carry out its orexigenic effect by

inhibiting excitatory input onto parvocellular neurons in the PVN. However, this effect is
eliminated in the presence of CB1R antagonist. This heavily implicates CB1Rs in the mediation
of ghrelin action. Not only is ghrelin unable to induce food intake in CB1R-KO mice, but in WT
mice an increase in ghrelin is associated with increased hypothalamic 2-AG levels18. Thus it is
thought that ghrelin acts through CB1Rs by promoting the production of cannabinoids such as
2-AG.
Peripheral Effects
Though many effects of cannabinoids are mediated through central pathways, there are
still some less-explored peripheral pathways as well. Ghrelin, released in the stomach, is one of
the peripheral hormones that is associated with feeding. In hedonic, or pleasure based,
feeding, palatable foods activate the reward circuitry via the release of DA, endocannabinoids
and opiates. Palatable food is also associated with an increase in peripheral ghrelin levels more
so than is observed with non-palatable food21. In addition to increased levels of ghrelin, 2-AG is
also present in higher levels following exposure to palatable foods. 2-AG levels are transiently
increased prior to feeding but decrease following ingestion of food21. Thus it can be inferred
that the peripheral levels of 2-AG in the small intestine and ghrelin within the stomach are
associated with hedonic feeding.
Though the association seems clear, the mechanism connecting olfactory processes and
feeding have not been extensively studied. It has been determined that CB1Rs are present in
the granule cell layer (GCL) of the olfactory bulb and that CB1R activation is required within the
main olfactory bulb (MOB) for hyperphagic response following fasting24. An increase in AEA

levels is associated with both increase in food intake and odor detection in a dose-dependent
manner24. It was determined that CB1R activation is necessary for the stimulation of appetite.
Peripheral cannabinoid levels are able to alter feeding. Specifically in the small intestine
there is a seven-fold increase in AEA levels following a 24 hour fast6. It was determined that
this increase in cannabinoid levels was not due to a decrease in AEA degradation, thus
indicating an increase in synthesis as the cause. After peripheral sensory terminals in the gut
were destroyed the CB1R agonist and antagonist actions no longer impacted food intake6.
Thus, peripheral cannabinoid receptor activation is necessary to stimulate food intake.
Discussion
There are many mechanisms that come together in order to promote feeding. It has
become evident that Δ-THC produces a clear orexigenic effect through CB1Rs. Cannabinoids
however do not carry out this effect alone. They work with opioids, leptin, ghrelin, MCH, and
the olfactory system. As expected, in most cases cannabinoids activate orexigenic components
and inhibit anorexigenic components. Of note is the fact that both leptin and cannabinoids are
able to regulate POMC neurons. This provides a new narrative for POMC neuron's role in the
regulation of food intake. Based on the results of the studies discussed it is likely that leptin
and cannabinoids are able to induce the release of different neuropeptides from POMC
neurons. Leptin will induce the release of α-MSH while cannabinoids induce the release of ß-
endorphins. Leptin is able to decrease cannabinoid levels, and thus acts through multiple
pathways in order to inhibit food intake. Leptin itself promotes α-MSH release to inhibit food
intake while keeping cannabinoid levels low and preventing ß-endorphin release and in turn

decreasing stimulation of appetite. This correlation is likely of great importance and should be
explored further moving forward in an attempt to treat obesity.
Incorporating the information from this thesis it is evident that CB1R activation
throughout the body leads to stimulation of appetitive behavior. It is also important to note
that by inhibiting CB1R activation it is possible to combat the typical effects associated with
obesity. Through this thesis I was able to identify instances in which antagonizing CB1Rs
reversed the insensitivity to insulin and increase in body fat percentage. More extensive
studies of cannabinoid-associated food intake will shed light on the complexity of food intake
regulation and may introduce novel drug targets to combat obesity. Of note is the previously
discussed paradox of both decreased inhibitory and excitatory transmission. This needs to be
further studied in order to better understand how the food intake system is modulated by
cannabinoids. Perhaps the most effective approach will involve a cocktail of drugs that will
modulate the food-intake control system at different points. As we have noted the bimodal
regulation of POMC neurons may be a critical regulatory point in food intake. Perhaps by
titrating the levels of an agonist and an antagonist of leptin and cannabinoid receptors,
respectively, we may be able to succeed using a multi-drug approach to the disorder of obesity
in which many single-drug approaches have failed.
Acknowledgements
First and foremost I would like to thank Dr. Thomas Anastasio for providing me with the
opportunity to conduct this research. Through this opportunity I have been able to expand my
knowledge and was able to develop the skills necessary to complete a thesis of this nature and

be successful as I move forward in the research world. I would also like to acknowledge the
effort put forth to assist me through this process by MIP graduate student Shayan Tabe
Bordbar. The continuous support and input throughout the process allowed me to successfully
complete this thesis as well.
References
1 Bakkali-Kassemi, L., Ouezzani, S., Magoul, R., Merroun, I., Lopez-Jurado, M., & Errami, M.
(2010). Effects of cannabinoids on neuropeptide Y and β-endorphin expression in the rat
hypothalamic arcuate nucleus. British Journal of Nutrition Br J Nutr, 105, 654-660.
2 Cota, D., Marsicano, G., Tschop, M., Grubler, Y., Flachskamm, C., Schubert, M., . . . Pagotto, U.
(2003). The endogenous cannabinoid system affects energy balance via central
orexigenic drive and peripheral lipogenesis. The Journal of Clinical Investigation, 112(3),
423-431.
3 Cowley, M., Smart, J., Rubinstein, M., Cerdan, M., Diano, S., Horvath, T., . . . Low, M. (2001).
Leptin activates anorexigenic POMC neurons through a neural network in the arcuate
nucleus. Nature, 411, 480-484.
4 Di Marzo, V., Goparaju, S., Wang, L., Liu, J., Batkal, S., Jaral, Z., . . . Kunos, G. (2001). Leptin-
regulated endocannabinoids are involved in maintaining food intake. Nature, 410, 822-
825.
5 Foltin, R., Fischman, M., & Byrne, M. (1988). Effects Of Smoked Marijuana On Food Intake And
Body Weight Of Humans Living In A Residential Laboratory. Appetite, 11, 1-14.
6 Gomez, R., Navarro, M., Ferrer, B., Trigo, J., Bilbao, A., Del Arco, I., . . . De Fonseca, F. (2002). A
Peripheral Mechanism for CB1 Cannabinoid Receptor-Dependent Modulation of
Feeding. The Journal of Neuroscience, 22(21), 9612-9617.
7 Heek, M., Compton, D., France, C., Tedesco, R., Fawzi, A., Graziano, M., . . . Davis, H. (1997).
Diet-induced obese mice develop peripheral, but not central, resistance to leptin.
Journal of Clinical Investigation J. Clin. Invest., 99(3), 385-390.
8 Hentges, S., Low, M., & Williams, J. (2005). Differential Regulation of Synaptic Inputs by
Constitutively Released Endocannabinoids and Exogenous Cannabinoids. Journal of
Neuroscience, 25(42), 9746-9751.

9 Ho, J., Cox, J., & Wagner, E. (2007). Cannabinoid-induced hyperphagia: Correlation with
inhibition of proopiomelanocortin neurons? Physiology & Behavior, 92(3), 507-519.
10 Huang, H., Acuna-Goycolea, C., Li, Y., Cheng, H., Obrietan, K., & Pol, A. (2007). Cannabinoids
Excite Hypothalamic Melanin-Concentrating Hormone But Inhibit Hypocretin/Orexin
Neurons: Implications for Cannabinoid Actions on Food Intake and Cognitive Arousal.
Journal of Neuroscience, 4870-4881.
11 Jamshidi, N., & Taylor, D. (2001). Anandamide administration into the ventromedial
hypothalamus stimulates appetite in rats. British Journal of Pharmacology, 134, 1151-
1154.
12 Jo, Y., Chen, Y., Chua, S., Talmage, D., & Role, L. (2005). Integration of Endocannabinoid and
Leptin Signaling in an Appetite-Related Neural Circuit. Neuron, 48(6), 1055-1066.
13 Jung, K., Clapper, J., Fu, J., D'agostino, G., Guijarro, A., Thongkham, D., . . . Piomelli, D. (2012).
2-Arachidonoylglycerol Signaling in Forebrain Regulates Systemic Energy Metabolism.
Cell Metabolism, 299-310.
14 Kirkham, T., Williams, C., Fezza, F., & Marzo, V. (2002). Endocannabinoid levels in rat limbic
forebrain and hypothalamus in relation to fasting, feeding and satiation: Stimulation of
eating by 2-arachidonoyl glycerol. British Journal of Pharmacology, 136, 550-557.
15 Kirkham, T., & Williams, C. (2001). Synergistic effects of opioid and cannabinoid antagonists
on food intake. Psychopharmacology, 153, 267-270.
16 Koch, J. (2001). Δ9-THC stimulates food intake in Lewis rats: Effects on chow, high-fat and
sweet high-fat diets. Pharmacology Biochemistry and Behavior, 68, 539-543.
17 Koch, M., Varela, L., Kim, J., Kim, J., Hernandez-Nuno, F., Simonds, S., . . . Horvath, T. (2015).
Hypothalamic POMC neurons promote cannabinoid-induced feeding. Nature, 519, 45-
50.
18 Kola, B., Farkas, I., Christ-Crain, M., Wittmann, G., Lolli, F., Amin, F., . . . Korbonits, M. (2008).
The Orexigenic Effect of Ghrelin Is Mediated through Central Activation of the
Endogenous Cannabinoid System. PLoS ONE, 3(3), 1-8.
19 Mcgregor, I., Arnold, J., Weber, M., Topple, A., & Hunt, G. (1998). A comparison of Δ9-THC
and anandamide induced c-fos expression in the rat forebrain. Brain Research, 19-26.
20 Melis, M., Perra, S., Muntoni, A., Pillolla, G., & Gessa, G. (2004). Endocannabinoids Mediate
Presynaptic Inhibition of Glutamatergic Transmission in Rat Ventral Tegmental Area
Dopamine Neurons through Activation of CB1 Receptors. Journal of Neuroscience, 24(1),
53-62.

21 Monteleone, P., Piscitelli, F., Scognamiglio, P., Monteleone, A., Canestrelli, B., Marzo, V., &
Maj, M. (2012). Hedonic Eating Is Associated with Increased Peripheral Levels of Ghrelin
and the Endocannabinoid 2-Arachidonoyl-Glycerol in Healthy Humans: A Pilot Study. The
Journal of Clinical Endocrinology & Metabolism, 97(6), 917-924.
22 Quarta, C., Bellocchio, L., Mancini, G., Mazza, R., Cervino, C., Braulke, L., . . . Pagotto, U.
(2010). CB1 signaling in forebrain and sympathetic neurons is a key determinant of
endocannabinoid actions on energy balance. Cell Metabolism, 11, 273-285.
23 Sinnayah, P., Jobst, E., Rathner, J., Caldera-Siu, A., Tonelli-Lemos, L., Eusterbrock, A., . . .
Cowley, M. (2008). Feeding Induced by Cannabinoids Is Mediated Independently of the
Melanocortin System. PLoS ONE, 3(5), 1-12.
24 Soria-Gomez, E., Bellocchio, L., Reguero, L., Lepousez, G., Martin, C., Bendahmane, M., . . .
Masricano, G. (2014). The endocannabinoid system controls food intake via olfactory
processes. Nature Neuroscience, 17(3), 407-415.
25 Trillou, C., Arnone, M., Delgorge, C., Gonalons, N., Keane, P., Maffrand, J., & Soubrié, P.
(2002). Anti-obesity effect of SR141716, a CB1 receptor antagonist, in diet-induced
obese mice. American Journal of Physiology - Regulatory, Integrative and Comparative
Physiology Am J Physiol Regul Integr Comp Physiol, 284, 345-353.
26 Trillou, C., Delgorge, C., Menet, C., Arnone, M., & Soubrié, P. (2004). CB1 cannabinoid
receptor knockout in mice leads to leanness, resistance to diet-induced obesity and
enhanced leptin sensitivity. Int J Obes Relat Metab Disord International Journal of
Obesity, 28, 640-648.
27 Wiley, J., Burston, J., Leggett, D., Alekseeva, O., Razdan, R., Mahadevan, A., & Martin, B.
(2005). CB 1 cannabinoid receptor-mediated modulation of food intake in mice. British
Journal of Pharmacology, 145, 293-300.

Cannabinoids Effect on Food Intake_Why Pot Gives You Munchies

Recommended

Recommended

More Related Content

Viewers also liked

Viewers also liked (12)

Similar to Cannabinoids Effect on Food Intake_Why Pot Gives You Munchies

Similar to Cannabinoids Effect on Food Intake_Why Pot Gives You Munchies (20)

Cannabinoids Effect on Food Intake_Why Pot Gives You Munchies