top of page

Overview of AMYLOIDOSIS  

In medicine, amyloidosis refers to a variety of conditions in which amyloid proteins are abnormally deposited in organs and/or tissues.   Amyloidosis may be inherited or acquired.  It can occur as its own entity or "secondarily" as a result of another illness, including multiple myeloma, chronic infections (such astuberculosis or osteomyelitis), or chronic inflammatory diseases (such as rheumatoid arthritis and ankylosing spondylitis).  Amyloidosis can also be localized to a specific body area from aging.  This localized form of amyloidosis does not have systemic implications for the rest of the body.  The protein that deposits in the brain of patients with Alzheimer's disease is a form of amyloid.

Systemic amyloidosis has been classified into three major types that are very different from each other. These are distinguished by a two-letter code that begins with an A (for amyloid).  The second letter of the code stands for the protein that accumulates in the tissues in that particular type of amyloidosis.  The types of systemic amyloidosis are currently categorized as primary (AL), secondary (AA), and hereditary (ATTR).

Primary amyloidosis:

Primary amyloidosis, or AL, occurs when a specialized cell in the bone marrow (plasma cell) spontaneously overproduces  a particular protein portion of an antibody called the light chain. (This is why it is coded as AL).   The deposits in the tissues of people with primary amyloidosis are AL proteins.  Primary amyloidosis can occur with a bone marrow cancer of plasma cells called multiple myeloma.  Primary amyloid is not associated with any other diseases but is a disease entity of its own, conventionally requiring chemotherapy treatment.  Researchers at the Mayo Clinic in Rochester, Minnesota, and Boston University in Boston, Massachusetts, have demonstrated benefits from stem-cell transplantation, harvesting patients' own stem cells to treat primary amyloidosis.


Secondary amyloidosis:

When amyloidosis occurs "secondarily" as a result of another illness, such as multiple myeloma, chronic infections (for example, tuberculosis or osteomyelitis), or chronic inflammatory diseases (for example, rheumatoid arthritis and ankylosing spondylitis), the condition is referred to as secondary amyloidosis or AA.  The amyloid tissue deposits in secondary amyloidosis are AA proteins.  The treatment of patients' secondary amyloidosis is directed  at treating the underlying illness in that particular patient.


Familial amyloidosis:

Familial amyloidosis, or ATTR, is a rare form of inherited amyloidosis.  The amyloid deposits in familial amyloidosis are composed of the protein transthyretin, or TTR, which is made in the liver.  Familial amyloidosis is an inherited autosomal dominant in genetics terminology.  This means that for the offspring of a person with the condition, there is a fifty percent  chance of inheriting it.


Beta-2 microglobulin amyloidosis:

Beta-2 microglobulin amyloidosis occurs when amyloid deposits develop in patients on dialysis with longstanding kidney failure.  The amyloid deposits are composed of beta-2 microglobulin protein and are often found around joints.
Localized amyloidoses:
The many forms of localized amyloidosis are a result of amyloid deposits in specific areas of the body and are distinct from systemic forms of amyloidosis that deposit amyloid throughout the body.  Localized amyloid deposits occur in the brain from Alzheimer's disease.   In various tissues, often with aging, amyloid can be locally produced and deposited to cause tissue injury.


Signs and Symptoms:

The signs and symptoms of amyloidosis depend on the location and size of the amyloid deposits.
AL may affect any tissue.  Signs and symptoms may be vague and can include the following:

  • Heart disease and irregular heart beat more than one-third of patients with AL have a heart condition

  • Stroke

  • Kidney disorders, including kidney failure

  • Gastrointestinal (GI) disorders, such as perforation (hole), bleeding, slow movement of matter through the GI tract, and blockage

  • Enlarged liver

  • Diminished function of the spleen

  • Diminished function of the adrenal and other endocrine glands

  • Skin conditions, such as growths, color changes, purpura (bleeding into the skin) around the eyes, and easy bruising

  • Enlarged tongue, sometimes with swelling under the jaw, breathing difficulties, and sleep apnea

  • Lung problems

  • Swelling of the shoulder joints (may look like shoulder pads under the skin)

  • Bleeding problems


Signs and symptoms of hereditary amyloidosis may include the following:

  • Nervous system disorders

  • Gastrointestinal conditions, such as diarrhea and weight loss

  • Heart problems

  • Carpal tunnel syndrome

  • Kidney disease, though this is less common than in AL


Signs and symptoms of secondary amyloidosis may include the following:

  • Kidney disease, which may lead to kidney failure; this is the cause of death in 40 - 60% of cases.

  • Enlarged liver

  • Enlarged spleen

  • Heart problems this is rare, and less severe than in other forms of amyloidosis.
    Most people who are diagnosed with AA have had their related inflammatory disease for a decade or more.

Findings: Effects of Cannabis on Inclusion Body Myositis and AMYLOIDOSIS

THC prevents formation of amyloid plaques.  Cannabis inhibits B-amyloid peptide aggregation.  Cannabinoids have  immunomodulatory properties (helpful in neuroinflammatory diseases).  THC suppresses cell-mediated immune responses.  THC is a neuroprotector and an analgesic.  CBD reduces inflammation, anxiety and nausea.  CBN is a weak agonist of CB1R and CB2R.  Most well known endocannabinoids are:  anandamide and 2-arochidonoyl glycerol-both are neuurotransmitters and both are synthesized "on demand" through multiple biosynthetic pathways.  CB2 interferes with inflammation cytokin release and blocks or modulates microglial cells.  In the 400 plus compounds in cannabis, 66 are CB's.  Cannabinoids are antioxidants.

Several recent studies have suggested that the endocannabinoid system (ECS) participates in brain immune control and neuroprotection, playing a crucial role in the cellular communication network in and between the nervous and immune system during persistent glial activation and neuronal damage.  Therefore, the cannabinoid system may represent a new, promising field of research, because many cell types involved in AD neuropathology express components of this system, which can be endogenously or pharmacologically modulated (Pazos et al., 2004).  Recent results showing remarkable changes of endocannabinoid levels and receptor concentrations in patients' brains and in experimental models have further reinforced the assumption that this system is substantially dysregulated in AD (Benito et al., 2003).  In rat hippocampus, the same authors revealed that Aβ induced a selective 2-fold enhancement of 2-arachidonoyl glycerol (2-AG) along with a significant up-regulation of CB2, but not CB1, receptors concomitant with the onset of neuronal damage markers (van der Stelt et al., 2006).  Further evidence, showing that CB1 receptor-selective activation inhibits inducible nitric-oxide synthase expression and blunts tau protein hyperphosphorylation in Aβ-challenged rat neuronal cells (Esposito et al., 2006), has suggested putative neuroprotective and antiinflammatory properties of ECS.
All these findings have encouraged research on the effects of ECS manipulation on Aβ-induced reactive astrogliosis, because it may help identify potential targets.

Marijuana and its active constituent, {Delta}9-tetrahydrocannabinol (THC), suppress cell-mediated immune .   Many of these effects are mediated by the cannabinoid receptor 2 (CB2), as demonstrated by the finding that THC inhibits helper T-cell activation by normal, but not CB2 knockout-derived, macrophages . While many studies have investigated effects of cannabinoids on immune function, few studies have examined their effects on the CD40 pathway

Activated microglial cells have been implicated in a number of neurodegenerative disorders, including Alzheimer's disease (AD), multiple sclerosis (MS), and HIV dementia.  It is well known that inflammatory mediators such as nitric oxide (NO), cytokines, and chemokines play an important role in microglial cell-associated neuron cell damage.  Previous studies have shown that CD40 signaling is involved in pathological activation of microglial cells.  Many data reveal that cannabinoids mediate suppression of inflammation in vitro and in vivo through stimulation of cannabinoid receptor 2 (CB2).

Cannabinoids have been found to have antioxidant properties , unrelated to NMDA receptor antagonism. This new found property makes cannabinoids useful in the treatment and prophylaxis of wide variety of oxidation associated diseases, such as ischemic, age-related, inflammatory and autoimmune diseases.  The cannabinoids are found to have particular application as neuroprotectants, for example in limiting neurological damage following ischemic insults, such as stroke and trauma, or in the treatment of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and HIV dementia. Nonpsychoactive cannabinoids, such as cannabidoil, are particularly advantageous to use because they avoid toxicity that is encountered with psychoactive cannabinoids at high doses useful in the method of the present invention.  A particular disclosed class of cannabinoids useful as neuroprotective antioxidants is formula (I) wherein the R group is independently selected from the group consisting of H, CH3, and COCH3. ##STR1##

The orphan G protein coupled receptors, GPR55 and GPR18, are both activated by a variety of exogenous and endogenous cannabinoids and lipids, including the cannabidiol analogue, abnormal cannabidiol (abn-CBD), AEA and N-arachidonoyl glycine. Both GPR55 and GPR18 have been suggested as candidate receptors for the abn-CBD-sensitive cannabinoid-related receptor that mediates hypotension and alterations in macrophage activity.
There is a growing body of evidence that inflammation and inflammatory disorders, including sepsis, could be modulated by endogenous chemical signaling molecules such as lipid mediators.  The fundamental role of lipid mediators is regulating resolution of inflammation through activation of anti-inflammatory and pro-resolving signaling pathways.

The ECS plays an important role in immune system modulation and increasing evidence supports upregulation of the ECS during both local and systemic inflammation, e.g. sepsis. Endocannabinoids are released from macrophages, dendritic cells, platelets and parenchymal cells in response to inflammatory stimuli and oxidative stress, and are present in elevated levels in the sera of patients and animals in septic shock.
Examination of CBR function has revealed that CB2R are present on macrophages, neutrophils and lymphocytes and activation of these receptors has been generally associated with anti-inflammatory effects including reduced macrophage and neutrophil numbers at the site of infection and decreases in pro-inflammatory cytokines. 

'Cannabinoids from the plant, Cannabis sativa, have been widely used in medicine for over a millennium as anticonvulsant, analgesic, anti-emetic, anti-inflammatory and immunosuppressive drugs'.  The recent interest in cannabinoids was triggered by the discovery of endogenous cannabinoid receptors and their ligands, anandamide and 2-arachidonoyl glycerol (2-AG).  Cannabinoid-1 receptors (CB1R) exist primarily on central and peripheral neurons, their major role is to modulate neurotransmitter release, whereas the cannabinoid-2 receptors (CB2R) are found mainly on immune cells and are known to play a role in immune response and regulation of inflammatory processes.  The endocannabinoid system (ECS) is upregulated during local and systemic inflammation.  However, the role of the ECS in the immune response is still not completely known.  Cannabinoid receptors activate multiple signaling pathways  including preferential activation of Gi proteins, inhibition of adenyl cyclase (AC) and reduction in cAMP accumulation, and activation of mitogen activated protein kinase pathways in most tissues.  In the nervous system, CB1R activation results in inhibition of voltage-dependent calcium channels, as well as both activation and inhibition of voltage-dependent potassium channels.

In summary, inflammatory diseases, including sepsis, are characterized by pathological changes within the microcirculation.  Long-lasting impairment of the microcirculation causes severe decrements in tissue perfusion and organ function and plays a key role in the progression to severe sepsis.  Given the complex pathophysiology of systemic inflammation and the high mortality associated with severe sepsis, identifying novel drugable targets and appropriate therapeutic windows is a priority for treating this disease.

During the last decade, research has identified the ECS as a key regulator of essential physiological functions, including the regulation of microvascular and immune function.  Indeed, increasing evidence now suggests that release of endocannabinoids and activation of cannabinoid receptors occurs during sepsis and that manipulation of the ECS may represent an important therapeutic target in managing sepsis and septic shock.  However, in order to move these findings into the clinic, it still remains essential to provide a more comprehensive understanding of ECS activity during sepsis.  This will require further examination of: 1) ECS function in relevant experimental models of inflammation and sepsis using appropriate techniques, such as IVM. 2) Identification of target receptor proteins (both cannabinoid and non-cannabinoid receptors) involved in mediating the actions of cannabinoids and endocannabinoids in both immune cells and microvasculature.  This information will increase our comprehension of the role of lipid signaling pathways in inflammation and may lead to the identification of new drug targets for treating sepsis.

Within the immune system, it has been shown that endo-CBs are upregulated in conditions of  in?ammation, that they downregulate the functionality of several types of human and rodent immunocytes,
and that this anti-infection/anti-inflammatory action is largely mediated through CB2R activation.
Activation of the CB2R attenuates proliferation of T- cells, activation of macrophages, and cytokine production; enhances proliferation of B cells, retaining immature precursor cells in the bone marrow;
The CB2R is closely associated with the immune system, being prevalent in peripheral immune cells, such as white blood cells.  Also, CB2R mRNA has been localized in the spleen, tonsil, and thymus, organs that are important sites of immune cell production and regulation.
CBD also acts as an analgesic and muscle relaxant.  In addition, it appears to have anticonvulsant, anxiolytic, neuroprotective, and antioxidant properties.  Most importantly, although it has effects on the central nervous system, CBD is virtually without psychotropic actions and indeed may be an antipsychotic.

We are only just beginning to appreciate the therapeutic potential of CBs.  To realize the therapeutic potential suggested by preclinical data, it is likely that, in managing the symptom burden in CKD, both CB1R and CB2R agonists, alone or in combination with each other and/or with CBD, and ultimately, the endo-CB system, will have to be completely studied (using real samples of medical grade marijuana).

Use Medical Marijuana as adjunct to pharmaceuticals (doctor recommendations).  You may begin to use less of the pharmaceuticals!

Use extracts of Indica x Sativa hybrids  (higher levels of CBC, CBD, CBG, CBN, THC) to treat symptoms.  Extracts (glycerin, oil, alcohol)

Vaporizer:  (am Sativa dominant)    (pm Indica dominant)

Supporting Research:

Bastianetto S, Ramassamy C, Doré S, Christen Y, Poirier J, Quirion R. The Ginkgo biloba extract (EGb 761) protects hippocampal neurons against cell death induced by beta-amyloid. Eur J Neurosci. 2000;12(6):1882-1890.
Beers MH, Porter R, eds. The Merck Manual of Diagnosis and Therapy. 18th ed. Whitehouse Station, NJ: Merck Research Laboratories; 2006:1310-12.
Buxbaum J. Treatment and prevention of the amyloidoses: can the lessons learned by applied to sporadic inclusion-body myositis? Neurology. 2006;66(2 Suppl 1):S110-3.
Falk RH, Skinner M. The systemic amyloidoses: an overview. Adv Intern Med. 2000;45:107-137.
Goldman L. Inherited and metabolic hepatic disorders. Cecil Textbook of Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2008:1436-7;2083-7.
Kholova I, Kautzner J. Current treatment in cardiac amyloidosis. Curr Treat Options Cardiovasc Med. 2006;8(6):468-73.
Lebrazi H, Hachulla E, Saile R. Treatments for amyloidosis beyond symptomatic care [in French]. Rev Med Interne.2000;21(3):247-255.
Lim GP, Calon F, Morihara T, Yang F, Teter B, Ubeda O, Salem N Jr, Frautschy SA, Cole GM. A diet enriched with the omega-3 fatty acid docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model. J Neurosci. 2005 Mar 23;25(12):3032-40.
Liu F, Lau BH, Peng Q, Shah V. Pycnogenol protects vascular endothelial cells from beta-amyloid-induced injury. Biol Pharm Bull. 2000;23(6):735-737.
Morena M, Cristol J, Canaud B. Why hemodialysis patients are in a prooxidant state? What could be done to correct the pro/antioxidant imbalance. Blood Purif. 2000;18(3):191-199.
Sezer O, Eucker J, Schmid P, Possinger K. New therapeutic approaches in primary systemic AL amyloidosis. Ann Hematol.2000;79(1):1-6.
Wettstein A. Cholinesterase inhibitors and ginkgo extracts -- are they comparable in the treatment of dementia?Phytomedicine. 2000;6(6):393-401.
Zubkov A, Rabinstein A, Dispenzieri A, Wijdicks E. Primary systemic amyloidosis with ischemic stroke as presenting complication. Neurology. 2007;69(11):1136-41.


1. 01. Vincent JL, Rello J, Marshall J, Silva E, Anzueto A, Martin CD, et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA - J Am Med Assoc 2009;302:2323-9.
2. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001;29:1303-10.
3. Angus DC, Wax RS. Epidemiology of sepsis: an update. Crit Care Med 2001;29(7 Suppl):S109-16.
4. Monneret G, Venet F, Pachot A, Lepape A. Monitoring immune dysfunctions in the septic patient: a new skin for the old ceremony. Mol Med 2007;14:64-78.
5. Hanus LO. Pharmacological and therapeutic secrets of plant and brain (endo) cannabinoids. Med Res Rev 2008;29:213-71.
6. Pertwee RG, Ross RA. Cannabinoid receptors and their ligands. Prostag Leukotr Ess 2002;66:101-21.
7. Varga K, Wagner JA, Bridgen DT, Kunos G. Platelet- and macrophage-derived endogenous cannabinoids are involved in endotoxin-induced hypotension. FASEB J 1998;12:1035-44.
8. Marshall JC, Deitch E, Moldawer LL, Opal S, Redl H, Poll T van der. Preclinical models of shock and sepsis: what can they tell us? Shock 2005;24 Suppl 1:1-6.
9. Remick DG, Ward PA. Evaluation of Endotoxin Models for the Study of Sepsis. Shock 2005; 24 Suppl 1:7-11.
10. Deitch EA. Rodent models of intra-abdominal infection. Shock 2005;24 Suppl 1:19-23.
11. Remick DG, Newcomb DE, Bologos GL CD. Comparison of the mortality and inflammatory response of two models of sepsis: lipopolysaccharide versus cecal ligation and puncture. Shock 2000;13:110-6.
12. Weinstein WM, Onderdonk AB, Bartlett JG, Gorbach SL. Experimental intra-abdominal abscesses in rats: development of an experimental model. Infect Immun 1974;10:1250-5.
13. Bartlett JG, Onderdonk AB, Louie T, Kasper DL, Gorbach SL. A review. Lessons from an animal model of intra-abdominal sepsis. Arch Surg 1960;113:853-7.
14. Hansson L, Alwmark A, Christensen P, Jeppsson B, Holst E BS. Standardized intra-abdominal abscess formation with generalized sepsis: pathophysiology in the rat. Eur Surg Res 1985;17:155-9.
15. Wichterman KA, Baue AE. Sepsis and septic shock: a review of laboratory models and a proposal. J Surg Res 1980;29:189-201.
16. Lustig MK, Bac VH, Pavlovic D, Maier S, Grundling M, Grisk O, et al. Colon ascendens stent peritonitis--a model of sepsis adopted to the rat: physiological, microcirculatory and laboratory changes. Shock 2007;28:59-64.
17. Ince C. The microcirculation is the motor of sepsis. Crit Care 2005;9 Suppl 4:S13-9.
18. Klijn E, Den Uil CA, Bakker J, Ince C. The heterogeneity of the microcirculation in critical illness. Clin Chest Med 2008;29:643-54.
19. Lehmann C, Georgiew A, Weber M, Birnbaum J, Kox WJ. Reduction in intestinal leukocyte adherence in rat experimental endotoxemia by treatment with the 21-aminosteroid U-74389G. Intens Care Med 2001;27:258-63.
20. Nencioni A, Trzeciak S, Shapiro NI. The microcirculation as a diagnostic and therapeutic target in sepsis. Intern Emerg Med 2009;4:413-8.
21. De Backer D, Ospina-Tascon G, Salgado D, Favory R, Creteur J, Vincent J-L. Monitoring the microcirculation in the critically ill patient: current methods and future approaches. Intens Care Med 2010;36:1813-25.
22. Chierego M, Verdant C, De Backer D. Microcirculatory alterations in critically ill patients. Minerva Anestesiol 2006;72:199-205.
23. Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008;36:296-327.
24. Birnbaum J, Klotz E, Spies CD, L

bottom of page