Endocannabinoids Critical for Brain Function

Back In NatureEndocannabinoids are derived from fatty acids in a very complex process. They serve as critical signals for a wide variety of brain functions. “Endo” refers to cannabinoids made in the brain, as opposed to “phytocannabinoids” made in plants and ingested. For simplicity, this post will use the general term “cannabinoids” when referring to the two endocannabinoids critical for brain function—AEA and 2-AG. 

A previous post described the extremely elaborate system of fatty acid derivatives that are critical signaling molecules. Two specific fatty acids, DHA and ARA, enter the brain and cellular membranes where they attach to phospholipids for storage and await release by special enzymes. One in 10,000 of these fatty acids are unattached to the membrane lipoproteins and are actively metabolized into many important signals through the mysterious Land cycle. One well-known derivative of ARA is prostaglandin, a vital part of N0019835 Cell membrane with different receptor typesthe inflammation response. Perhaps, the most important derivatives are cannabinoids that are critical for neuron and glia function. In the fetus, cannabinoid signals determine the fate of neuronal stem cells and glia and then switch to become the critical factors in the creation of the synapses for the developing brain. They are vital for every aspect of the creation of the structure of the fetal brain including directing neuron migration and axons and dendrite development.

A tremendous amount of progress has been made in understanding production of proteins from DNA and RNA. Because of this, genes can be “knocked out” (eliminated) and the effects of specific proteins can be studied. No such technology exists to study fatty acids, which are commonly part of many very complex metabolic cycles. As a result, it is extremely difficult to study how these thousands of different molecules are used in metabolic energy metabolism, as structural molecules, and as signals for vital brain functions. While known to be extremely important for all brain functions, fatty acid signaling is just now being described.

This post will outline what is currently known about these vital brain cannabinoids.

Two Vital Cannabinoids

The most important and abundant cannabinoid for the neuronal system is 2-AG (2-arachidonoylglycerol) and the second is AEA (anandamide or N-arachidonoylethanolamine.) Both of these, and many other fat signals, stimulate the two cannabinoid receptors CB1 and CB2. They, also, stimulate other important families of fatty acid receptors. AEA has variable effects on receptors both partially stimulating and partially antagonist.

Endocannabinoid

Endocannabinoid

Neurotransmitters dopamine, acetylcholine, serotonin and glutamate NMDA stimulate enzymes that cut ARA and DHA free from their attachment to membrane lipoproteins in neurons and glia. Then, they are metabolized in the not well-understood Land cycle to make derivatives and mediators. This process is highly regulated to make many vital brain signals. The Land cycle utilizes 5% of all of the brain’s energy. It is stimulated whenever these molecules are needed, such as in brain development, memory in adults, ischemia, brain injury and inflammation.

Mediators from DHA and ARA

From Quibik

From Quibik

DHA and ARA metabolites regulate changes in the cell membrane (see post on the Amazing Complexity of the Cellular Membrane). They stimulate complex protein kinase C (PKC) and inhibit the nuclear factor, NF-κβ.

One mediator derived from ARA is prostaglandin by the enzyme COX – (cyclooxygenases) as part of the inflammation response. Many other enzymes work in this cycle, such as LOX and P450, which call for leukocytes and the cleaning of debris. Prostaglandin is a very strong inflammation signal and is inhibited by the well-known NSAID medications for inflammation and pain. Other derivatives regulate the hypothalamus to produce glucose from the liver related to food intake.

Cannabinoids are very important derivatives of ARA and DHA. Most often, they travel from the postsynaptic neuron to the pre synaptic in retrograde fashion and regulate processes in the synapse. Cannabinoids and their receptors are manufactured by neurons, astrocytes and microglia. These bind to the CB1 and CB2 receptors, which regulate release of glutamate, GABA, monoamines, opiods and acetylcholine. They are critical in neuroplasticity for excitatory and inhibitory synapses.

Wide Range of Cannabinoid Effects

B0002882 Trimeric G protein/adenylate cycl. surf.pot.The details are just being discovered, but cannabinoids are known to be important for pain sensation, appetite, memory, motor learning, neuroplasticity and mood. CB1 and CB2 trigger large G proteins that lie just below the cell membrane of cells in the brain, peripheral neurons and immune cells. These send signaling cascades to the nucleus to trigger genetic networks.

As well as memory, appetite and neuroplasticity, cannabinoid signals are critical for balancing metabolic systems. They regulate hunger and interact with the amount of leptin in the blood. They bring into balance storage and transport of nutrients and energy storage in fat, intestinal, muscle and pancreas cells.

Insulin secretionCannabinoids are involved in the complex regulation of insulin, the cortisol stress response and the hypothalamus-pituitary-adrenal system. When stress continues, anandamide produces tonic secretion of cortisol. If stress is repeated many times then 2-AG is secreted in the amygdala, lowering cortisol. These changes are related to anxiety. In animals, cannabinoid receptors on glutamate neurons are related to aggression and anxiety.

In the immune system, cannabinoids modulate both neurons and immune cells. They protect against inflammation and muscle spasms in multiple sclerosis. Plant based cannabis have been used even in ancient times to help tremors and muscle spasms as well as modern research with animals.

bigstock-Pain in back   -concept-or-con-43945414Cannabinoids are involved in modulating pain sensation. They decrease responses from the dorsal horn after painful stimuli, possibly by regulating the secretion of norepinephrine from the locus coeruleus in the pons. This modulation occurs by inhibiting GABA fibers in the spinal cord, causing more norepinephrine. Another fatty acid related to AEA—palmitoylethanolamide—is involved in the pain pathways through multiple receptors other than CB1 and CB2.

In adults, 2-AG is made in the postsynaptic cell near the postsynaptic density. Stimulation of the postsynaptic receptors and calcium stimulate 2-AG to form. It, then travels back across the synapse to the pre synaptic cell triggering CB1 receptors. This stops more activity in the synapse. It is then de activated by lipid enzymes. Astrocytes, also, have this lipid enzyme to stop 2-AG.

AEA function is more complex. It can inhibit the synapse in the same way as 2-AG or it can be made in the pre synaptic neuron, which then behaves like a more typical neurotransmitter and goes to the post synaptic cell.

Critical Cannabinoid Actions in The Fetus 

B0001014 Foetal MRI scanThe fetal brain builds multiple signaling pathways for neurons and glial cells that interact in very complex ways. The cannabinoid signals determine new neurons and glia from stem cells, neuron polarity for migration and axon production and the formation of the synapses in the cortex. They, also, build the pattern of neuronal connections. 

In the fetus, morphogenic signals create gradients determining the structures of very complex tissues. Progress has been made in understanding these morphogens from protein signaling, but they, also, use many lipids signals that are less understood, including sphingolipids, glycolipids, prostanoids and cannabinoids.  

In fetal tissue, cannabinoids can function in autocrine mode, that is, they are secreted in the same cell as the receptor that is triggered. This provides stimulus for stem cells to multiply. The manufacture of both cannabinoids and receptors are in different places in the stem cell, with the receptors within lipid rafts in the membrane.

They, also, use paracrine secretion where cannabinoids are secreted from one cell to another, often retrograde across the synapse. This is used to attract axons and dendrites to make synapses, oligodendrocytes to make myelin and to help with neuron and axon migration.

Cannabinoids Signals Create Fetal Brain Structures

B0007285 Human brain cellsThe cannabinoid signals are critical to making new neurons for the developing brain and the structures that they form. There are specific regions where important signals are produced during the complex process of axon growth, including dendrite spines and growth cones of axons. Early neuron stem cells create both CB1 and CB2. In the fetus, CB2 is very common in the stem cells of the cortical subventricular zone, a region that makes new neurons in adults. Cannabinoids stimulate stem cells to make new neurons rather than more stem cells, and then trigger neuron migration.

Once the stem cell has committed to forming a neuron, then CB2 manufacture stops and only CB1 is manufactured and utilized. The CB1 makes the cell polarized, which stimulates migration and long axon growth. Pyramidal cells in the cortical plate (precursor of the cortex) make 2-AG that defines positions where the neuron will form in the structure.

B0006219 Human embryonic stem cellAfter stem cells make more neurons, widespread cannabinoid signaling throughout the region stimulates production of many glia cells. The large amount of cannabinoid signals helps many neurons find their way in the migrations forming the cortex. These interactions between the various neurons are just being uncovered but are extensive. They may provide the direct guidance for movement.

To maintain the growing structure, specific enzymes are de activated, which limit cannabinoid signaling as the neuronal connection structure forms. These cannabinoid signals, also, affect the radial glia, which form the basic scaffolding structure on which the cortical neuronal network forms. The radial glia form a 3D checkered pattern, which then limits more cannabinoids that would alter the structure.

Another critical fetal structure built by cannabinoids is the basic sensory long tracts between the cortex and the thalamus. The enzymes that control cannabinoids sculpt the amount of neurons and axons needed. CB1, also, creates the pattern of interneurons.

Fetus Receptor Signals

FEATURE Microglia  iStock_000006935562SmallWhen making the cortex with stem cells and migrating neurons, 2-AG antagonizes neurons through CB1, which controls the radial travel of pyramidal cells and the lateral movement of interneurons.

When making dendrites and synapses, many other factors stimulate 2-AG, which alter the internal scaffolding skeleton of the neurons, which are forming the axon and dendrite. The cannabinoid receptors can be altered by specific factors to make them positive and negative. An important example is when the neurons from the thalamus and the cortex meet and CB1 positive and CB1 negative attract each other. Through this attraction, digitations are formed for the synapse by many elaborate signaling cascades.

Gradual Change from AEA to 2-AG

AEA is necessary for the embryo implantation and continued survival of the fetus. But, then, as the nervous system develops, 2-AG becomes the prominent signal. Cannabinoids determine the amount of neural stem cells and are critical to signal the need to make more neurons rather than astrocytes. This depends on a switch from CB2 to CB1.

B0001869 Purkinje cells and radial gliaGABA interneurons are directed by 2-AG and avoid enzymes that will degrade them. There appear to be special cannabinoid gradients that are used for migration of these interneurons. Special enzymes that make and degrade the cannabinoids direct the gradients.

CB1 receptors on the growing axons are related to internal cytoskeletal alterations necessary for the rapidly growing axons and dendrites. Locations of the 2-AG are highly specialized to provide direction for the very complex 3D travel of the axon throughout the organizing brain. The positive and negative versions of the receptors are critical for attraction and repulsion in this travel.

Once the synapse forms, then the enzymes regulating cannabinoids are dramatically altered. One is then stationed in the dendrite region and the other in the axon.

Glia Cannabinoids

B0006137 Schwann cell myelinating axonsCannabinoid lipid signaling is critical for making new astrocytes and oligodendrocytes, as well. All of the same enzymes are found in both cells. For oligodendrocytes, the mechanism uses a neurotransmitter and a receptor in the same cell. This increases the number of glia stem cells. Cannabinoid signaling between cells (cannabinoid and receptor from different cells) attract astrocytes and oligodendrocytes to particular regions. In this way glia are attracted to make myelin for the long neuronal axons as they develop. 

Ingestion of Plant Cannabinoids during Pregnancy

From Axsadi

From Axsadi

Although cannabinoids are critical for development of the nervous system, they can react to new circumstances and change very rapidly. Studies in animals show that giving cannabinoid antagonists stop the travel of early neurons from the subventricular zone by altering significant wiring structures. Cannabinoid agonists, also, are disruptive by increasing the number of cells in particular regions.

Since cannabinoid signaling is highly regulated by neurotrophic factors, and many different enzymes, ingested cannabinoids have subtle wide range effects on different neurons and synapses that are not well understood.

In humans, babies exposed during pregnancy can develop compulsions and depression, as well as decreased visual memory. Animal studies show dramatic effects in very young babies. In mice, adolescents are affected, as well, with decreased social behavior and learning.

Cannabinoids In Adults 

Cannabinoids have different functions in the adult brain and therefore affects of ingested plant cannabinoids are very different in the established adult brain. 

From ActiveDendrite

From ActiveDendrite

In adults, cannabinoids stimulate the creation of new neurons in the adult brain, in the hippocampus, the subventricular and olfactory zones. Because of this, research has focused on the possibility of using cannabinoids to stimulate new brain cells after brain damage.

In adult synapses, AEA and 2-AG are controlled by multiple unique enzymes and transporters both at the cell membrane and inside multiple different compartments inside the cell. They are related to heat shock proteins and lipid storage organelles. There is a major intracellular system for cannabinoids that involves many different compartments that are just now being discovered. Many of the transporters have been identified, but not the exact compartments. These compartments, also, exist outside of the cell on both presynaptic and post synaptic neurons, microglia and astrocytes.

The major niche for new neurons in the adult is in the hippocampus and the subventricular zone of the lateral ventricle where the neurons travel a long distance to the olfactory bulb. Research shows that in the dentate nucleus of the hippocampus new neurons are related to new memories. After brain damage, neurons from the subventricular zone travel to the damaged regions and the striatum.

B0000502 Neurons in hippocampusThere are several powerful growth factors that are signals for new neurons and regulate stem cells division and resting periods. The stem cells are ready to go in either direction as stimulated by cannabinoids. Surprisingly, cannabinoid stimulation of new neurons by stem cellss occurs more powerfully in the elderly brain.

2-AG is the main cannabinoid stimulating new neurons in adults. Blocking it decreases new neurons in the hippocampus. This effect is either by cells stimulating their own receptors or by stimulating other cells. It is not clear how and where cannabinoids maintain the readiness of stem cells to make new neurons.

Conclusions of this research are the existence of a dynamic process in the adult brain where cannabinoids maintain neuroplasticity and keep stem cells ready to make new neurons. The system responds rapidly to injury, degenerative brain disease, inflammatory brain disease and depression. Cannabinoids provide stimulus for new neurons and directions for their travel in the brain. Research has shown that stimulating neurogenesis is part of the cure of depression. The response to damage is less certain.

Astrocyte Cancer

N0009762 MRI scan; brain cancer (glioma)The most prominent cannabinoid known in the marijuana plant is Δ9 –tetrahydrocannabinol, known as THC. THC stimulates the CB receptors in stem cells that make new neurons as well as the neurons themselves. These affects appear to be different in adults, adolescents and children. It is possible that manipulating these pathways in treatments might increase new neurons and affect out of control neuronal and glioma cancers.

Glioblastoma is a malignant cancer of astrocytes, with a mechanism of cancer growth tied to lipids in the membrane. In animals, cannabinoids have stopped cancers of glia cells through stimulation of cell death of tumor cells without hurting normal cells. The stimulation of CB receptors, also, affects metastasis and blood vessel production for the cancer. In humans CB2 receptors and calcium channels are increased in the glioma. Clinical trials using cannabinoids in treatment of human cancers are now being done.

The mechanism has to do with stressing the endoplasmic reticulum until the tumor cell dies. AEA, also, causes cell death of cancers from neuroblastoma, astroglia and oligodendroglia cells

It is not clear how cannabinoids can stimulate the production of new neurons and glia stem cells, but kill glia tumor cells. The lipid cycles and pathways are too complex at present to understand this dramatic and significant difference. 

Endocannabinoids Critical for Brain Function

Cannabinoids are fatty acid molecules derived from the polyunsaturated free fatty acids ARA and DHA through a very complex and poorly understood process. Among many fatty acid signals in the brain, cannabinoids are vital to the developing brain in many ways and adult brain function including memory and neuroplasticity. Cannabinoids, and their receptors, are manufactured by neuronal and glia stem cells, neurons, astrocytes, microglia and oligodendrocytes.

B0005622 Enhanced MRI scan of the headThere is no current technology to study free fatty acids that is equivalent to the very detailed knowledge of proteins through knockout of genes. Free fatty acids are ubiquitous in cells in metabolic cycles for all types of functions. But, it is now clear that they are, also, critical neurotransmitters and neuromodulators. Lipid signaling (as well as glyco signaling) adds an enormous amount of new complexity for understanding brain function. 

Surprisingly, cannabinoids stimulate neuronal stem cells to make new neurons in adults, and at the same time kill brain cancer cells. The mechanism of this major difference is not clear.

When stem cells both secret cannabinoids and then trigger their own receptors stimulating the production of more stem cells, where is the direction for this? This is a question equivalent to how cells know how to self edit their own DNA.

Cannabinoids are an exciting area for future research.

This entry was posted in Blog, Neuronal Plasticity, Cellular Intelligence, Human Brain and tagged , , , , , , , , . Bookmark the permalink.
  • Oldfart

    I see exactly NO references to published peer-reviewed studies. In fact, I see no reference to clinical studies at all. I find is AMAZING that humans could ever have developed at all without smoking pot. According to this tirade, at least.

    • repealit1975

      yes there should be links. but Endo = produced inside the body. clear now how we could develop without cannabis?

      • Oldfart

        If THC is produced inside the body, what do we need pot for?

        In the following section of Wikipedia, all the research has been done on rats or in vitro. There are no human studies mentioned:

        https://en.wikipedia.org/wiki/Endocannabinoid_system#Functions_of_the_endocannabinoid_system

        • Tom

          No, AEA and 2-AG are produced in the body, the plant Cannabinoid THC mimics human AEA, and CBD mimic human 2-AG.

          The medicinal value in THC & CBD comes from the fact that, although they mimic human cannabinoids, they are not 100% identical!

          This is CRUCIAL to their effectiveness, because, Science tells us that our body breaks down our own AEA & 2-AG very quickly, where as, because the ‘reverse’ side of THC is NOT the same as AEA (i.e. one side of THC activates our receptors, but the reverse side is ALIEN!), thus, the enzymes that normally break down our natural cannabinoids have a very hard time breaking down and getting rid of plant Cannabinoids.

          This means the plant Cannabinoids ‘stimulate’ our CB receptors for HOURS rather than SECONDS!

          If it were the case that plant Cannabinoids were 100% identical to our own, we would likely needs BUCKET loads ofthe stuff to treat a condition! 🙂

          This fantastic quirk of evolution, that THC, CBD, and other plant Cannabinoids ‘mimic’ but are not 100% identical to our own, and the fact that means they take much longer for our body to get rid of… is the reason Cannabis has any notable effect at all!

          Love nature!

          • Oldfart

            I get your religious fervor. However, nothing of what you said proves that weed cures anything. Yet. I say ‘Yet” because scientists have not had access to pot in this country (the USA) long enough to study it. Even today there are very few studies of the curative or healthful effects of pot on anything. and few long term studies. Your religious statements lack scientific evidence just like any religious claim.

          • 1garryminor3

            In 1936 a Polish Anthropologist named Sula Benet discovered that in the original Hebrew text of the Old Testament the word “kaneh bosm”(קְנֵה-בֹשֶׂם) was translated as “calamus” or fragrant cane by the Greeks when they first rendered the Books in the 3rd century B.C., then propagated as such in all future translations from the original Greek without review, including Martin Luthers. During that same time period Hebrew slowly ceased to be used as a spoken language. It wasn’t until the late 1800’s that a man named Eliezer Ben-Yehuda revived it once again. Benet concluded through years of substantial research and etymological comparison that the correct translation of “kaneh bosm” should be “cannabis.” In 1980 the Hebrew Institute of Jerusalem confirmed her claim that indeed “kaneh bosm” is cannabis. Ben-Yehuda’s 1964 Hebrew-English dictionary confirms this fact, page 140. The Biblical “Canon,” from the Greek “Kanon,” meaning; “to measure, to rule, straight, upright,” is also derived from the Hebrew word “kaneh”(קְנֵה). In fact we now know that all early religions used cannabis and, or, other psychotropic plants as sacraments. Calamus was used by ancient peoples and still today as an aphrodisiac and stimulant, its active chemical asarone is a precursor to the psychedelic MDMA, ecstasy. ……..
            In Exodus 30:23 GOD instructs Moses to use 250 shekels of “kaneh bosm” in the oil for anointing all Priests, and later Kings and Prophets, for all generations to come, including that of Jesus and even today as the title Christ/Messiah means literally; “covered in oil, Anointed.” “Kaneh” is also listed as an incense tree in Song of Songs 4:14. The error was repeated in Isaiah 43:24, Jeremiah 6:20, and Ezekiel 27:19, where “kaneh, kaneh bosm” are translated as calamus or sweet cane. There are 141 references to the anointing and 145 to burning incense in the standard Bible.

            Much has been learned regarding the role of cannabis and human development since Benet discovered the error over seventy years ago, and with these revelations along with the discovery of the Dead Sea Scrolls, Nag Hammadi Library, certain Apocrypha, and a closer examination of the Bible, we find that in order to be called worthy of the title “Christian” one has to be anointed with the very Holy Oil as described in the original Hebrew text of Exodus. Johns water baptism is incomplete and any other oil counterfeit. Jesus came to free the restricted Holy Oil and make Anointed Priests of all men with ears to hear his message, baptizing with fire and the Holy Spirit, the “Chrism.” The Anointing is symbolic of being baptized in the “Holy Spirit.” It is synonymous with the Laying on of hands and also called the Seal, Unction, and Counselor. It is “the Way.” Under the old covenant Priests were ordained to stand between God and the people, Jesus died so that all believers could become Anointed Priests before the Lord. A chosen people, a royal Priesthood, a Holy nation. Ex 40:12-16, 1 Peter 2:4-10, Rev 1:6, 5:10, 20:6

            A few examples. Read, the Book!!!

            1 Samuel 16:13;
            So Samuel took the horn of oil and anointed him in the presence of his brothers, and from that day on the Spirit of the LORD came upon David in power. Samuel then went to Ramah.
            For the rest of the story; Cannabis, Christ and the Word of God

            http://columbuzz.net/submitted/godrelated/3897.html

            Garry Minor
            Columbus Kaneh Bosm Ministry
            Columbus Indiana

            Early Diffusion And Folk Uses Of Hemp: Dr. Sula Benet
            http://web.acsalaska.net/~warmgun/sm410.html

            Cannabis and its Preparations in Saga, Science and Sobriquet: Dr. Ethan Russo
            http://csatc.org/linksofinterest/Russo2007.pdf

            Cyril of Jerusalem: On Chrism
            http://www.ccel.org/ccel/schaff/npnf207.ii.xxv.html

          • Goodtimes

            ^ that was amazing.

          • Oldfart

            LOL! The Bible is NOT a source of scientific evidence about anything other than the gullibility of mankind.. Nor is any other religious text for that matter.

          • 1garryminor3

            What it must be like to live in such Spiritual poverty? Old fart?

            AlterNet;
            Pot Shrinks Tumors; Government Knew in ’74
            http://www.alternet.org/drugs/9257

            Here is the 1974 Virginia study regarding the ability of cannabis to destroy tumors.
            “Unfortunately, the world bumps along between such moments of hope and long periods of intellectual castration.”

            http://www.ukcia.org/research/AntineoplasticActivityOfCannabinoids/index.php

            Here is the 2000 study by Guzman, twenty six years later, almost fifteen years ago, that proves the same. How sad! 1600 Americans a day die of cancer! Little children!

            http://herb.com/guzman.pdf

            And; “Cannabis destroys cancer cells… reveals research at Barts and The London, Queen Mary’s School of Medicine and Dentistry”

            http://drsircus.com/medicine/cancer/cannabis-destroys-cancer-cells

            And; “Here, we review recent work that raises interest in the development and exploration of potent, nontoxic, and nonhabit forming cannabinoids for cancer therapy.”

            http://m.cancerres.aacrjournals.org/content/68/2/339.full

            Prior to becoming illegal in 1937, “cannabis tinctures, fluid extracts, and flowers” were the most commonly used medicines in the USA. Your great-grandparents would have used them! (This information was deleted from the pharmacopoeia in 1941)

            http://antiquecannabisbook.com/chap4/Tincture.htm

            http://www.new-territory.net/cann_uses.txt

            Dr. Andrew Weil: Cannabis Rx: Cutting Through the Misinformation (Even colicky babies were treated with cannabis medicines)

            http://www.huffingtonpost.com/andrew-weil-md/can-cannabis-treat-cancer_b_701005.html

            Alzheimer’s; “Our results indicate that cannabinoid receptors are important in the pathology of AD and that cannabinoids succeed in preventing the neurodegenerative process occurring in the disease.”

            http://www.jneurosci.org/content/25/8/1904.full

            Traumatic Brain Injury; (2002) “We expect that within the next few years these mechanisms will be clarified and cannabinoid-based drugs for brain trauma will be introduced in the clinic.”

            http://www.lycaeum.org/research/researchpdfs/2002_mechoulam_1.pdf

            MRSA; “Everything points towards these compounds having been evolved by the plants as antimicrobial defenses that specifically target bacterial cells,” says Gibbons. “But the actual mechanism by which they kill the bugs is still a mystery.”

            http://www.technologyreview.com/news/410815/a-new-mrsa-defense/

            MS; “Therefore, in addition to symptom management, cannabis may also slow the neurodegenerative processes that ultimately lead to chronic disability in multiple sclerosis and probably other diseases.”

            http://m.brain.oxfordjournals.org/content/126/10/2191.full

            Neurogenesis; “Thus, cannabinoids appear to be the only illicit drug whose capacity to produce increased hippocampal newborn neurons is positively correlated with its anxiolytic- and antidepressant-like effects.”

            http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1253627/

            Autism; (outstanding) “It was like a wave of calmness just swept over him and he changed from being a monster into a loveable, little boy.”

            http://www.letfreedomgrow.com/cmu/SamsStory.htm

            Aids; New research proves cannabinoids suppress the virus!

            http://dx.plos.org/10.1371/journal.pone.0033961

            http://www.hivandhepatitis.com/hiv-aids/hiv-aids-topics/hiv-treatment/267,313-hiv-alternative-complementary-therapy-hiv-alternative-complementary-therapy/3530-cannabinoids-may-inhibit-cd4-cell-infection-by-cxcr4-tropic-hiv

            Retinal function; “A team led by scientists from the University of California, San Diego (UCSD) has demonstrated the prevalence of cannabinoid receptors in the retina, indicating an important role for cannabinoids—a family of compounds which includes the psychoactive components of marijuana and hashish—in retinal function and perhaps vision in general.”

            http://ucsdnews.ucsd.edu/newsrel/health/potpnas.htm

            Not to mention ALS, ADHD, OCD, PTSD, epilepsy, diabetes, obesity, depression, tuberculosis, lupus, nausea, migraine, arthritis, alcoholism, drug addiction, cystic fibrosis, anxiety, glaucoma, chronic pain, fibromyalgia, asthma, emphysema, anorexia, muscular dystrophy, meningitis, flu, gut and eating disorders, herpes, Huntingtons, Tourettes, Parkinsons, Crohns disease, and many more!

            Hemp Seed Nutrition;
            The most nutritionally complete food source on earth!
            “Seeds of the plant cannabis sativa, hemp seed, contain all the essential amino acids and essential fatty acids necessary to maintain healthy human life. No other single plant source has the essential amino acids in such an easily digestible form, nor has the essential fatty acids in as perfect a ratio to meet human nutritional needs.”

            http://www.ratical.org/renewables/hempseed1.html

            1938-1941 Popular Mechanics.
            Build a car from the soil! American jobs! What happened?

            http://www.ukcia.org/research/PopularMechanics/index.php

            How about this?
            “You wouldn’t read about it… Lotus have gone for a different type of ‘green’ by announcing an ‘Eco Elise’ made largely out of hemp!”

            http://www.transport20.com/uncategorized/lotus-announces-hemp-based-eco-elise-a-new-type-of-green-car/

            A Battery Made of Hemp
            Environmentalists have long championed the eco-friendly virtues of hemp, but more recently engineers have discovered the plant’s energy-saving properties. Researchers in the U.S. have developed a super-strong, super-fast, hemp-based battery called a supercapacitor that could charge things like electric cars and power tools and is a cheaper alternative to conventional graphene supercapacitors, researchers say.

            http://m.ibtimes.com/battery-made-hemp-plant-based-supercapacitor-better-graphene-study-finds-1657512

            Look at all we’ve been deprived of!!!
            And this is only the tip of the iceberg!
            Then, you have the Spiritual deprivation!

            Sorry folks, but, there has been a huge deception, the Keys to the Kingdom have remained hidden, just as the prophets predicted, and, it says in Revelation, the institution and foundation of the churches of the world are literally and Biblically:
            anti- opposite of, opposed to or against
            Christ- covered in Holy Oil, Anointed.
            1John 2:18-29
            Nice people, just lacking the True Chrism, the Holy Spirit!

            Jesus said, “The [Father’s] kingdom is like a woman who was carrying a [jar] full of meal. While she was walking along [a] distant road, the handle of the jar broke and the meal spilled behind her [along] the road. She didn’t know it; she hadn’t noticed a problem. When she reached her house, she put the jar down and discovered that it was empty.”
            Gospel of Thomas

            The Answer!

            “The chrism is superior to baptism, for it is from the word “Chrism” that we have been called “Christians,” certainly not from the word “baptism.” And it is because of the “Chrism” that the “Christ” has his name. For the Father anointed the Son, and the Son anointed the Apostles, and the Apostles anointed us. He who has been anointed possesses everything. He possesses the resurrection, the light, the cross, the Holy Spirit. The Father gave him this in the Bridal chamber, he merely accepted the gift. The Father was in the Son and the Son in the Father. This is the Kingdom of Heaven.”
            Gospel of Philip

            Nag Hammadi Library
            http://gnosis.org/naghamm/nhl.html

          • Oldfart

            Thanks for the Gish Gallop.

            I will only respond to a few of them because one is not required to waste time with idiots and true believers by responding to a Gish Gallop. The Gish Gallop technique is used by creationists to attack real scientiests which gives you an indication where YOU fall in the scheme of things. It’s equivalent to throwing feces at a wall to see what sticks.

            #1 is a post in alternet.org which is not a peer-reviewed publisher of scientific studies.

            #2 A quote from #2: “Lewis lung adenocarcinoma growth was retarded by the oral administration of delta-9-tetrahydrocannabinol, delta-8-tetrahydrocannabinol, and cannabinol (CBN), but NOT CANNABIDIOL (CBD). ” My emphasis.

            #3 is a .pdf file. Who knows where it came from? Or where it was published. Or IF it was published as a peer-reviewed study.

            #4 is an article on a web site appropriately named “Dr. Sircus” .com that references a study of some kind but never gives a link to the study or to the journal it was supposedly published in or anything else much. It just makes a few unsupported claims.

            #5 to quote the abstract: “Cannabinoids are a class of pharmacologic compounds that offer potential applications as antitumor drugs, based on the ability of some members of this class to limit inflammation, cell proliferation, and cell survival. In particular, emerging evidence suggests that agonists of cannabinoid receptors expressed by tumor cells may offer a novel strategy to treat cancer. Here, we review recent work that raises interest in the development and exploration of potent, nontoxic, and nonhabit forming cannabinoids for cancer therapy. ”

            Note the use of the words potential, suggests,may offer, raises interest. In other words, this is a study which does not definitely prove that cannabinoids DO anything except that they are worth further research.

            And so on, and so on. This is the bible on which your religion is based. You keep worshipping and I’ll wait for the real science.

          • 1garryminor3

            Old fart!
            Blah blah blah!
            How much do they pay you to make such ignorant remarks?
            You must either work for big pharmakeia or our government!
            Talk about being controlled!
            Regardless, you are free to believe whatever you want!
            I pity you!
            Again! What it must be like to to live in your hylic, Spiritual darkness?
            You are incapable of understanding, and therefore, want everyone to be as miserable as you are!
            I know that you aren’t able to see this, but, you need to wash your pants! You soiled yourself!
            Anyone that needs to hide behind such a mindless avatar as “old fart” isn’t worth the time of day!
            Gather your gang and enjoy lounging in your “scientific” ignorance!
            Meanwhile, 1600 Americans will suffer and die today of cancer because of heartless, mindless, self-righteous people like you!
            Time will tell who is correct!
            Kaneh Bosm

          • Oldfart

            You really are an ignorant idiot, aren’t you. I don’t work for ANYBODY in the medical field, pharma field, regulation field. NONE of them. But, I AM a rational human being who depends on science and not magic to interpret the reality around me. As for spiritual darkness. LOL. YOU believe in things that don’t have any provable existence and have no concept of the wonder of the real world. For some poor reason, possibly a genetic defect, you require fairies to tell you what to believe. Meanwhile, thousands of believers like you will die this year thanks to the snake oil salesmen you believe in. And even more will die around the world because of people like you refusing to deal with reality. I don’t feel sorry for you at all. Darwin will take care of you.

          • 1garryminor3

            Like I said!
            You are Not capable of understanding!
            You are a hylic!
            You don’t even understand evolution!
            Please, go away!
            You’re getting old ….. fart!
            What a joke!

  • Greg Carmello

    cannabis has been proven to kill cancer cells , and reduce toumers, cannabis stimulates our endocannabinoid system, and causes our immune system to kick in and fight many diseases

  • Greg Carmello

    Google Rick Simpson

  • Niklas

    And so subjective mind makes war on itself. Peace comes when you realize there are no subjects. Only objects acting “as if” separate.
    Take your seat gents, and be mindful of how you become believers in your Egos. That can be ecperienced you know.
    Meditate.
    Evolve.
    Peace.

  • Shredder

    The fact that some prohibitionist troll came slammin’ around here tells me this subject worries them. Therefore, time to push push push. Thanks Oldfart! We’re going to bring lots more attention to this and make sure the good words gets out.

  • Mary Clinton

    They say its a matter of when ill die but Im open to any estudies. Its flat on my brain so when lifted will RIP off brain. Has rotos. Dr at sammons in Dallas. I dont want to die but cant stand living like this

  • Ed Bland

    The reason that I keep posting how MARIJUANA is healing my brain is because it was used DECEITFULLY !
    ~ Eaten THC brings the body’s “PH” level up to 7.2 where CANCER “DIES”.
    ~ This is an OPEN invite to TEST my brain to take to court to “change” MARIJUANA laws !
    ~ HUMANS do not realize that it is LOVE of “earth” that I do this !
    The FEDS do not realize that I am a very high I.Q. person with medical background.
    Do you really want such LOW INTELLIGENCE running this NATION when they can’t even see the TRUTH ?
    On 08-30-2008 I wrecked my motorbike with no helmet on. It killed me 3 times in life flight putting me into an 87 day coma waking with a recorded 5.5 brain injury requiring me to go through rehabs relearning life. Once I returned home I had a friend ask me to get a medical card and try CANNABIS. I was amazed because not only did my memories start returning but my thought process was working again. This made me research why. I found that THC reduces blood vessels while making the heart pump harder making blood go to the injured brain. Head rushes are proof.

  • Charles Ancient Convert Ankner

    Very well done Doctor, well researched and articulated. Now, what about cannabinoids as sedation agents for anesthesia and non-lethal weapons? https://www.linkedin.com/pulse/weaponized-cannabis-tm-charles-ankner?trk=prof-post

  • Anthony Cicalla Junior

    This is my facebook page with all of the published studies. This will get you started. Please pass to drake and zeek.

    https://www.facebook.com/pages/St-Jude-Research-Hospital-Memphis-Tennessee-Cannabis-kills-leukemia/1432340060320604?ref=bookmarks

    kill lung cancer
    http://www.ncbi.nlm.nih.gov/pubmed/22198381

    http://www.bravemykayla.com/

    Cannabis oil cures baby of an Inoperable Brain Tumor says Dr. William Courtney
    http://www.youtube.com/watch?v=DqHassCMX-0

    THC Affects on cancer and normal brain cells
    http://www.youtube.com/watch?v=3OqSRfzqwWA&authuser=0

    US Patent Application 20100222437
    Gastrointestinal inflammatory and cancers
    http://www.google.com/patents/US20100222437

    US Patent Application 20100204312
    Treating cell proliferation and cancers
    http://www.google.com/patents/US20100204312

    US Patent Application 20080262099
    Inhibition of tumour cell migration
    http://www.google.com/patents/US20080262099

    US Patent 6410588
    Cannabidiol and inflammatory diseases
    http://www.google.com/patents/US6410588

    US Patent 8071641
    Diabetes and insulitis
    http://www.google.com/patents/US8071641

    US Patent 8242178
    Cannabidiol and autoimmune hepatitis
    http://www.google.com/patents/US8242178

    US Patent Application 20080181942
    Multiple sclerosis and MS relapse
    http://www.google.com/patents/US20080181942

    US Patent Application 20090197941
    Chronic Obstructive Pulmonary Disease
    http://www.google.com/patents/US20090197941

    Jan., 2013 National Cancer Institute PDQ® report on cannabis:

    http://www.cancer.gov/cancertopics/pdq/cam/cannabis/healthprofessional/page2

    Dr. William Courtney Benefits of juicing raw cannabis.

    http://www.youtube.com/watch?v=eRLVyGfGcZs

    Cures Cancer in General
    http://www.ncbi.nlm.nih.gov/pubmed/12514108
    http://www.ncbi.nlm.nih.gov/pubmed/15313899
    http://www.ncbi.nlm.nih.gov/pubmed/15313899

    Cures Bladder Cancer
    http://www.medscape.com/viewarticle/803983 (Sign-up required to view study)

    Cures Biliary Tract Cancer
    http://www.ncbi.nlm.nih.gov/pubmed/19916793

    Cures Liver Cancer
    http://www.ncbi.nlm.nih.gov/pubmed/21475304

    Cures Skin Cancer
    http://www.ncbi.nlm.nih.gov/pubmed/12511587

    Curse Blood Cancer
    http://www.ncbi.nlm.nih.gov/pubmed/12091357
    http://www.ncbi.nlm.nih.gov/pubmed/16908594
    http://onlinelibrary.wiley.com/doi/10.1002/ijc.23584/abstract
    http://molpharm.aspetjournals.org/content/70/5/1612.abstract

    Cures Ovarian Cancer
    http://www.aacrmeetingabstracts.org/cgi/content/abstract/2006/1/1084

    Cures Colorectal Cancer
    http://www.ncbi.nlm.nih.gov/pubmed/22231745

    Cures Prostate Cancer
    http://www.ncbi.nlm.nih.gov/pubmed/12746841?dopt=Abstract
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3339795/?tool=pubmed
    http://www.ncbi.nlm.nih.gov/pubmed/22594963

    Cures Uterine, Testicular, and Pancreatic Cancers
    http://www.cancer.gov/cancertopics/pdq/cam/cannabis/healthprofessional/page4
    http://cancerres.aacrjournals.org/content/66/13/6748.abstract

    Cures Lung Cancer
    http://www.ncbi.nlm.nih.gov/pubmed/22198381?dopt=Abstract
    http://www.ncbi.nlm.nih.gov/pubmed/21097714?dopt=Abstract
    http://www.nature.com/onc/journal/v27/n3/abs/1210641a.html

    Cures Breast Cancer
    http://www.ncbi.nlm.nih.gov/pubmed/20859676
    http://www.ncbi.nlm.nih.gov/pubmed/18025276
    http://www.ncbi.nlm.nih.gov/pubmed/21915267
    http://jpet.aspetjournals.org/content/early/2006/05/25/jpet.106.105247.full.pdf+html
    http://www.molecular-cancer.com/content/9/1/196
    http://www.ncbi.nlm.nih.gov/pubmed/22776349
    http://www.pnas.org/content/95/14/8375.full.pdf+html

    Cures Mouth and Throat Cancer
    http://www.ncbi.nlm.nih.gov/pubmed/20516734

    Cures Brain Cancer
    http://www.nature.com/bjc/journal/v95/n2/abs/6603236a.html
    http://www.ncbi.nlm.nih.gov/pubmed/11479216
    http://www.jneurosci.org/content/21/17/6475.abstract
    http://jpet.aspetjournals.org/content/308/3/838.abstract
    http://mct.aacrjournals.org/content/10/1/90.abstract

    U..S. Government Patent 6,630,507, “Cannabinoids as Antioxidants and Neuroprotectants”

    Fri, Mar 20, 2009 – 3:38 am — Thinking CAP In 2003, the United States Patent Office awarded the Department of Health and Human Services patent #6,630,507, “Cannabinoids as antioxidants and neuroprotectants.” (In case you don’t know, cannabis is another name for marijuana. AND in case you don’t know, neuroprotection means protection for your your brain, where there are many neurons, your spine, where there are also many neurons, and other aspects of your nervous system.) Here are some (layman-converted-for-laymen) excerpts from the abstract in the awarded patent:

    Cannabinoids have antioxidant properties… [Antioxidants prevent cellular damage: 1 | 2 | 3 | 4 ] This property makes cannabinoids useful in the treatment and prevention of a wide variety of oxidation associated diseases: inflammation, age-related diseases, autoimmune diseases, and lack of blood-flow to the brain.

    Cannabinoids are found to have particular application as neuroprotectants, for example in limiting neurological damage following lack of blood-flow to the brain, such as stroke and trauma, or in the treatment of neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease and HIV dementia.