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Marijuana is not the only way to activate your cannabinoid system.  There are more fundamental and gentle ways that help activate your cannabinoid system and bring you similar benefits.

Top 13 Ways to Increase Cannabinoids Without Smoking Pot


I don’t think it’s a coincidence that I respond well to every treatment that increases cannabinoid receptors.

1) Stress Reduction

Emotional stress decreases CB1 receptors [R], including social defeat stress [R].

Prolonged exposure to elevated glucocorticoids (cortisol), such as those induced by chronic stress conditions, significantly reduces hippocampal CB1 receptors [R], leading to lower cannabinoid function.

In fact, a recent study suggests that CB1 receptor deficiency may mimic the effects of chronic stress on emotional behavior [R].

2) Omega 6’s

Anandamide, 2-AG, 2-AGE, and other endogenous cannabinoids are derived from arachidonic acid.

Studies of piglets show that dietary levels of arachidonic acid and other essential fatty acids affect the levels of anandamide and other endocannabinoids in the brain [R]. High-fat diet feeding in mice increases levels of anandamide in the liver [R].

3) Exercise

Exercise increased the CB1 receptor sensitivity [R] and also increases anandamide, which is our natural CB1 activator [R].

4) Dietary Fats

A high-fat diet increases liver levels of the endocannabinoid anandamide (arachidonoyl ethanolamide) and increases CB1 receptors [R].

5-6) Nicotine or Galantamine

Activation of nicotinic receptors leads to increased cellular levels of calcium, which is known to stimulate the release of our natural cannabinoids such as anandamide [R].

Indeed, the CB1 receptor mediates some of the addictive and motivational aspects of nicotine [R].

Chronic nicotine treatment increases endocannabinoid levels in limbic regions [R].

7) Fish oil/DHA

DHA increases cannabinoid synthesis and CB1 and CB2 receptors [R].

8) Cold Exposure

Cold showers are quite relaxing and it does feel like you get a high when the shower is done.  It turns out that cold exposure stimulates the cannabinoid system [R, R, R].

9) Sun

Sun increases cannabinoid receptors indirectly. UVA is a potent inducer of nitric oxide in the body.

Nitric Oxide increases expression and abundance of CB1 receptors in mice [R].

10) Increase Testosterone

Testosterone and DHT increase the CB1 receptors [R].

11) Increase Estradiol

Estradiol increases anandamide, CB1 receptors and inhibits FAAH [R, RR], all of which help activate the cannabinoid system. (however, it increases FAAH gene expression [R]).

12) CBD Oil

Cannabidiol or CBD is the less psychoactive part of the cannabis plant.

CBD actually blocks the CB1 receptor and has the opposite effects of THC in some ways.

CBD has more of an indirect effect by increasing CB1 receptors [R] and inhibiting FAAH [R].

13) Butyrate

Butyrate increases CB1 gene expression – epigenetic histone acetylation has an important role in activation of the Cannabinoid system [R].

I suspect that stress and inflammation cause epigenetic changes to the cannabinoid system that might be able to be revered by butyrate.

Other Ways to Increase Cannabinoid Function

  1. Extra Virgin Olive Oil [R].
  2. Fructose, sugar, and carbohydrates [R].
  3. Resistant starch – HDAC inhibitors/histone acetylation [R].


  1. Calcium increases CB1 activity and transport of CB1 receptors in rats [R].
  2. Potassium increases CB1 activity and transport in rats [RR].
  3. Folate increases CB1 expression in mice [R].
  4. Vitamin A increases CB1 expression in humans [R, R].


  1. Progesterone increases CB1 expression in humans [R].
  2. Cortisol increases CB1 abundance in mice [R, R, R].
  3. Endorphins [R].
  4. Epinephrine increases CB1 activity in rabbits [R].

Cannabinoid-Like Molecules

  1. Oleamide [R]
  2. Chocolate – N-acylethanolamines (NAEs), N-linoleoylethanolamide and N-oleoylethanolamine  inhibit FAAH [R].
  3. Palmitoylethanolamide – enhances anandamide.


  1. Tea/EGCG* (Full agonist, Ki 33.6 μM) [R] – according to another group, flavonoid-type compounds (catechins, anthocyanidins, flavones) lead to negligible or very high Ki values, which likely reflect a nonspecific molecular denaturation of the protein surface rather than a functional binding interaction [R].
  2. Inositol* [R].
  3. Resveratrol* (retracted) [RR].
  4. Bile acids* increase CB1 abundance in mice [R], but they also decrease the reaction.
  5. Hydrogen peroxide increases gene expression in humans [R].
  6. Honokiol [R].
  7. Capsaicin (in chili) increases secretion in mice [R].
  8. Agmatine
  9. Genistein [R].
  10. Kava/yangonin [R].
  11. Kaempferol, 7-hydroxyflavone and 3,7-dihydroxyflavone have been shown to concentration-dependently inhibit anandamide hydrolysis in rat brain homogenates, albeit at relatively high concentrations (IC50 values between 2 and 10 mM). Nevertheless, the authors of these studies showed a preliminary structure-activity relationship with 7-hydroxyflavone (7-hydroxyflavone and 3,7-dihydroxyflavone have been shown to concentration-dependently inhibit anandamide hydrolysis in rat brain homogenates, albeit at relatively high concentrations (IC50 values between 2 and 10 mM). Nevertheless, the authors of these studies showed a preliminary structure-activity relationship with 7-hydroxyflavone [R].


  1. Aspirin – COX-2 inhibitors activate the CB1 receptor [R].
  2. Trichostatin A increases CB1 gene expression in humans [R, R].
  3. Tylenol [R].
  4. Caffeine can help with the stress-induced decrease in CB1 receptors [R].
  5. Benzodiazepines work in part through CB1 receptors [RR].
  6. Morphine increases CB1 expression in humans [R].
  7. Alcohol and acetaldehyde increase expression in mice [R].


  • Cyclic AMP increases CB1 activity and abundance in humans [R, R].
  • Cytokines such as IL-1b increase the CB1 receptor [R]. IL-4 (Th2 cytokine) also increases cannabinoid receptors [R].
  • Nf-kb, RARα and CB2 activation increase CB1 receptors [R].
  • IL-4, STAT5 (Th2), STAT6 (Th2), NFAT, NF-κB, AP-1, REST, RARα/γ and ERE increase transcription of CB1 receptors [R, R].
  • CRY1 is correlated to CB1 receptors [R].
  • LPS increases activity and abundance of CB1 receptors in mice [R].

What Decreases CB1 receptors (avoid):


  • Emotional stress [R].
  • THC Dependence [R].
  • Colorectal cancer [R].
  • Pregnenolone – inhibits CB1 signaling – negative allosteric modulator [R, R, R].
  • Choline, by methylating the gene in mice [R].
  • Methionine, by methylating the gene in mice [R].
  • Oxygen decreases expression in humans [R].
  • Glucose decreases expression in rats [R].
  • Silver decreases expression in humans [R].
  • Bile salts decrease reaction in animals [R]
  • Andrographis* [R].
  • Hydroxytyrosol [R].
  • Silicon dioxide decreases expression in humans [R].
  • Sulfur Dioxide [R].
  • Epinephrine decreases reaction and abundance in animals [RR].
  • Greater Celandine (R)


  • Ibuprofen decreases reaction in rats [R].
  • Morphine decreases reaction [R].
  • Fluoxetine (SSRI) decreases expression in rats [R].
  • Valproic acid decreases expression in humans [R, R].
  • Ketamine decreases expression in rats [R].


  • Methylation -reduces gene expression [R].
  • PPAR delta decreases Cannabinoid receptor expression [R].
  • PGE2 [R].
  • COX2 – converts anandamide [R].
  • Lipoxin A4 – negative allosteric modulator [R].
  • Pepcan-12 – negative allosteric modulator [R].

What Activates CB2 Receptors


  • Beta-caryophyllene – activates CB2 receptor [R].
  • CBD* [R].
  • THC [R].
  • Echinacea/alkylamides binds to the CB2 receptor [R].
  • Curcumin* (retracted) [R, R], (CB2, but antagonist to CB1 [R])
  • EGCG [R].
  • DIM (R)

Increases receptor/function:

  • DHA increases CB2 receptors (R).
  • Lactobacillus acidophilus (R)
  • Dietary fats and arachidonic acid increases expression (R)
  • Cyclic AMP* (increases activity and abundance) (R)
  • Calcium increases transport (R)
  • Progesterone* increases expression (R)
  • Trichostatin A increases expression  (R)

What Decreases CB2

  • Cyclic AMP decreases reaction (R)
  • Polyphenols decrease expression (R)
  • BPA decreases expression (R)
  • CBD decreases secretion (R)
  • Progesterone decreases abundance (R)
  • Silicon dioxide decreases expression (R)

Health Tools I Wish I Had When I Was Sick

At SelfHacked, it’s our goal to offer our readers all the tools possible to get optimally healthy. When I was struggling with chronic health issues I felt stuck because I didn’t have any tools to help me get better. I had to spend literally thousands of hours trying to read through studies on pubmed to figure out how the body worked and how to fix it.

That’s why I decided to create tools that will help others cut down the guesswork:

  • Lab Test Analyzer – a software tool that will analyze your labs and tell you what the optimal values are for each marker — as well as provide you with actionable tips and personalized health and lifestyle recommendations to help you get there.
  • SelfDecode – a software tool that will help you analyze your genetic data from companies such as 23andme and ancestry. You will learn how your health is being impacted by your genes, and how to use this knowledge to your advantage.
  • SelfHacked Secrets – an ebook where we examine and explain the biggest overlooked environmental factors that cause disease. This ebook is a great place to start your journey if you want to learn the essential steps to optimizing your health.
  • SelfHacked Elimination Diet course – a video course that will help you figure out which diet works best for you
  • Selfhacked Inflammation course – a video course on inflammation and how to bring it down
  • Biohacking insomnia – an ebook on how to get great sleep
  • Lectin Avoidance Cookbook – an e-cookbook for people with food sensitivities
  • BrainGauge – a device that detects subtle brain changes and allows you to test what’s working for you
  • SelfHacked VIP – an area where you can ask me (Joe) questions about health topics

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  • Richard

    I use Linoleic Acid in cold-pressed grape seed oil, with probiotics, to increase 2-AG. This treats my genetic epilepsy, which is caused by a mutation in the CACNA1H gene. I have partial absence and atonic seizures, as well as a myriad of other issues such as hypothyroidism, hypertension, hyperlipidism, vitamin D deficiency, pre-diabetes, pre-osteoporosis, etc that went with my mutation. This is the real deal.

  • Nejc

    What * means? That it is or it is not significant?

  • Mohammed Afikur Rahman

    Thank you for this article I am amazed at how in depth you have written it out, it is truly a splendid work of art, a masterpiece

  • NipsMahGee

    Wouldn’t a negative Allosteric Modulator up-regulate the CB1 receptor over time?

  • Richard Rosen

    You have sugar on the increases list and glucose on the decreases list. Isn’t that contradictory?

    1. Jason

      i believe fructose is the sugar found is fruits, and glucose is more processed sugar, like syrup, hard candies, or typical store bought sugar.

    2. Cristobal Ferryman

      Sorry Jason, that’s incorrect. SUCROSE (in cane sugar, for example) is broken down into both glucose and fructose. Fructose is indeed found in fruits as well as sucrose (however that wasn’t the question). Insulin is secreted primarily in response to elevated blood concentrations of glucose, not fructose, and insulin facilitates the entry of glucose into cells. Fructose is more likely to be converted to fat. I have to assume the fructose component of sucrose counteracts the glucose component.

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